(I) DNA can be damaged by radiation, chemicals, and other environmental factors which cells have developed mechanisms to repair. (II) There are direct repair systems like photoreactivation and base excision repair that remove damaged bases. (III) Nucleotide excision repair and mismatch repair pathways cut out the damaged DNA section and resynthesize the correct sequence. (IV) Double strand breaks are repaired by nonhomologous end joining or homologous recombination.
DNA repair system lecture that were prepered by Ph.D. students Mohammed Mohsen and Aliaa Hashim at microbiology department / college of medicine / babylon university.
DNA repair systems are essential for maintaining the integrity of genetic information. There are multiple pathways for repairing different types of DNA damage:
1) Mismatch repair corrects errors made during DNA replication by using methylation patterns to distinguish the template strand.
2) Base-excision repair involves DNA glycosylases that remove damaged bases, leaving abasic sites that are then repaired.
3) Nucleotide-excision repair removes larger distortions in the DNA double helix.
4) Direct repair mechanisms like photoreactivation can directly reverse some types of damage using light or chemical processes, without removing nucleotides. DNA repair pathways help prevent mutations and ensure fidelity of genetic information.
DNA can be damaged by a variety of processes,
some spontaneous
Damage caused by environmental agents.
Error occurs during Replication (introduction of mismatched base pairs such as G paired with T).
The cellular response to this damage includes a wide range of enzymatic systems that catalyze some chemical transformations in DNA metabolism.
All Cells Have Multiple DNA Repair Systems
Direct repair
Mismatch repair
Excision repair
Replication fork encounters an unrepaired DNA lesion
Introduction
Enzyme involve of DNA repair
Types of DNA repair
direct DNA repair
excision repair system
mismatch repair system
Conclusion
Reference
DNA polymerase –a class of enzyme to all synthesize 5’ to 3’ direction of nucleotides.
DNA polymerase I – a class of enzyme 1st isolated by Escherichia coli, and function is removes of RNA primers ,during DNA replication.
Helicase- any of a group of enzyme that unwind the two strand of DNA to facilitate DNA replication.
Exonuclease – an enzyme capable of cutting phosphodiester bonds between nucleotides located at an end of a DNA strand .
Endonuclease – an enzyme capable of cleaving phosphodiester bonds between nucleotide located internally in a DNA strand .
DNA ligase – a enzyme that fill the gap of nucleotides.
DNA is constantly damaged by environmental and cellular factors, causing over 100,000 lesions per day. To prevent disease, cells have multiple repair pathways including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. Base excision repair fixes small base damages through removal and replacement. Nucleotide excision repair removes larger helix-distorting lesions by cleaving and synthesizing new DNA. Mismatch repair recognizes and fixes errors made during DNA replication. Double-strand break repair uses either non-homologous end joining or homologous recombination to reconnect broken DNA ends. Defects in these pathways compromise genomic integrity and can cause cancer or other genetic disorders.
DNA repair is essential to prevent damage from impairing organism survival and potentially causing cancer. The main types of DNA repair are mismatch repair, direct repair, base-excision repair, and nucleotide-excision repair. Mismatch repair in E. coli involves the MutS, MutH, and MutL proteins detecting mismatches that are then repaired. Direct repair directly changes altered bases back to their original structures using enzymes like MGMT. Base-excision repair removes small base lesions using DNA glycosylases and polymerases. Nucleotide-excision repair removes bulky UV-induced DNA adducts by cleaving and removing the damaged strand.
This document discusses DNA repair mechanisms. It begins with an introduction to DNA damage and sources of damage like base modifications, replication errors, and radiation. It then covers the major DNA repair pathways: direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. Double strand break repair can occur through direct joining or homologous recombination. DNA damage checkpoints pause the cell cycle to allow for repair. Defects in repair pathways cause hereditary disorders like xeroderma pigmentosum and Werner syndrome.
DNA repair is a crucial process that cells use to fix mutations in DNA. The cell's DNA repair mechanisms continuously scan the genome to identify and repair mutations before they can harm the cell. There are several pathways for DNA repair, including direct repair, excision repair, mismatch repair, recombinational repair, and SOS repair. Direct repair directly reverts damaged nucleotides to their original structures, but can only repair a small number of damage types, like UV radiation-induced damage repaired by photoreactivation. Excision repair removes damaged nucleotides and uses the undamaged strand as a template for resynthesis. Mismatch repair fixes errors from DNA replication by recognizing mismatches and excising the incorrect segment. [END SUMMARY]
DNA repair system lecture that were prepered by Ph.D. students Mohammed Mohsen and Aliaa Hashim at microbiology department / college of medicine / babylon university.
DNA repair systems are essential for maintaining the integrity of genetic information. There are multiple pathways for repairing different types of DNA damage:
1) Mismatch repair corrects errors made during DNA replication by using methylation patterns to distinguish the template strand.
2) Base-excision repair involves DNA glycosylases that remove damaged bases, leaving abasic sites that are then repaired.
3) Nucleotide-excision repair removes larger distortions in the DNA double helix.
4) Direct repair mechanisms like photoreactivation can directly reverse some types of damage using light or chemical processes, without removing nucleotides. DNA repair pathways help prevent mutations and ensure fidelity of genetic information.
DNA can be damaged by a variety of processes,
some spontaneous
Damage caused by environmental agents.
Error occurs during Replication (introduction of mismatched base pairs such as G paired with T).
The cellular response to this damage includes a wide range of enzymatic systems that catalyze some chemical transformations in DNA metabolism.
All Cells Have Multiple DNA Repair Systems
Direct repair
Mismatch repair
Excision repair
Replication fork encounters an unrepaired DNA lesion
Introduction
Enzyme involve of DNA repair
Types of DNA repair
direct DNA repair
excision repair system
mismatch repair system
Conclusion
Reference
DNA polymerase –a class of enzyme to all synthesize 5’ to 3’ direction of nucleotides.
DNA polymerase I – a class of enzyme 1st isolated by Escherichia coli, and function is removes of RNA primers ,during DNA replication.
Helicase- any of a group of enzyme that unwind the two strand of DNA to facilitate DNA replication.
Exonuclease – an enzyme capable of cutting phosphodiester bonds between nucleotides located at an end of a DNA strand .
Endonuclease – an enzyme capable of cleaving phosphodiester bonds between nucleotide located internally in a DNA strand .
DNA ligase – a enzyme that fill the gap of nucleotides.
DNA is constantly damaged by environmental and cellular factors, causing over 100,000 lesions per day. To prevent disease, cells have multiple repair pathways including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. Base excision repair fixes small base damages through removal and replacement. Nucleotide excision repair removes larger helix-distorting lesions by cleaving and synthesizing new DNA. Mismatch repair recognizes and fixes errors made during DNA replication. Double-strand break repair uses either non-homologous end joining or homologous recombination to reconnect broken DNA ends. Defects in these pathways compromise genomic integrity and can cause cancer or other genetic disorders.
DNA repair is essential to prevent damage from impairing organism survival and potentially causing cancer. The main types of DNA repair are mismatch repair, direct repair, base-excision repair, and nucleotide-excision repair. Mismatch repair in E. coli involves the MutS, MutH, and MutL proteins detecting mismatches that are then repaired. Direct repair directly changes altered bases back to their original structures using enzymes like MGMT. Base-excision repair removes small base lesions using DNA glycosylases and polymerases. Nucleotide-excision repair removes bulky UV-induced DNA adducts by cleaving and removing the damaged strand.
This document discusses DNA repair mechanisms. It begins with an introduction to DNA damage and sources of damage like base modifications, replication errors, and radiation. It then covers the major DNA repair pathways: direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. Double strand break repair can occur through direct joining or homologous recombination. DNA damage checkpoints pause the cell cycle to allow for repair. Defects in repair pathways cause hereditary disorders like xeroderma pigmentosum and Werner syndrome.
DNA repair is a crucial process that cells use to fix mutations in DNA. The cell's DNA repair mechanisms continuously scan the genome to identify and repair mutations before they can harm the cell. There are several pathways for DNA repair, including direct repair, excision repair, mismatch repair, recombinational repair, and SOS repair. Direct repair directly reverts damaged nucleotides to their original structures, but can only repair a small number of damage types, like UV radiation-induced damage repaired by photoreactivation. Excision repair removes damaged nucleotides and uses the undamaged strand as a template for resynthesis. Mismatch repair fixes errors from DNA replication by recognizing mismatches and excising the incorrect segment. [END SUMMARY]
This document summarizes the mechanisms of DNA repair. It discusses various types of DNA damage including tautomerization, deamination, oxidation, alkylation, and pyrimidine dimers. The main DNA repair mechanisms are damage reversal, damage removal, and damage tolerance. Damage reversal includes photoreactivation and direct repair enzymes. Damage removal consists of base excision repair, nucleotide excision repair, and mismatch repair. Damage tolerance uses error-prone repair or double-strand break repair. Accumulation of unrepaired DNA damage over time contributes to aging.
DNA repair mechanisms identify and correct damage to DNA. There are two main types of DNA damage: endogenous damage caused by metabolic byproducts, and exogenous damage caused by external factors like radiation or toxins. The main DNA repair pathways are direct reversal, base excision repair, nucleotide excision repair, mismatch repair, nonhomologous end joining, and homologous recombination. These pathways utilize various enzymes to recognize damage, cut and remove damaged sections of DNA, and use undamaged DNA as a template for repair synthesis to restore the proper DNA sequence. Defects in certain DNA repair pathways can cause human diseases like xeroderma pigmentosum or Cockayne syndrome.
This document discusses DNA repair mechanisms, specifically nucleotide excision repair. It provides details on:
1) Nucleotide excision repair is a mechanism to repair DNA damage such as thymine dimers caused by UV light. It involves the uvrA, uvrB, uvrC, and uvrD genes which encode proteins that recognize distortions in DNA structure and cut out the damaged region for replacement.
2) If nucleotide excision repair fails, it can result in genetic disorders like xeroderma pigmentosum which increases skin cancer risk, or Cockayne syndrome which involves neurological issues.
The document discusses various types of DNA damage including deamination, depurination, UV light-induced T-T and T-C dimers, alkylation, oxidative damage, replication errors, and double-strand breaks. It then summarizes different DNA repair pathways such as base excision repair, nucleotide excision repair, mismatch repair, direct repair, recombination repair, and non-homologous end-joining. The SOS response in bacteria is also summarized as activating error-prone repair when normal repair pathways are overwhelmed.
DNA repair mechanisms are essential for maintaining genomic integrity. There are several pathways for repairing different types of DNA damage: mismatch repair fixes errors during DNA replication, base excision repair removes damaged bases, nucleotide excision repair replaces larger sections of damaged DNA, and double-strand break repair fixes breaks in both DNA strands. Defects in DNA repair genes can lead to increased cancer risks and genetic disorders like xeroderma pigmentosum and Fanconi anemia. Overall, DNA repair helps prevent mutations from being passed to new cells.
1) The document discusses various agents that can damage DNA like radiation, chemicals, and how the cell repairs this damage through mechanisms like base excision repair, nucleotide excision repair, mismatch repair, and strand break repair.
2) It also discusses several diseases associated with defective DNA repair systems like Xeroderma pigmentosum, Ataxia telangiectasia, Bloom syndrome, Cockayne's syndrome, and Trichothiodystrophy.
3) Each disease is characterized by specific clinical features that result from an inability to properly repair DNA damage.
This document discusses DNA damage and repair mechanisms. It begins by introducing DNA damage and its sources, including endogenous sources like reactive oxygen species and exogenous sources like radiation. It then describes different types of DNA damage such as single base alterations, double base alterations, chain breaks, and cross-linkages. The document proceeds to explain four main DNA repair pathways: photoreactivation, base excision repair, nucleotide excision repair, and mismatch repair. Each repair pathway involves specific enzymes to identify and remove damaged DNA and allow for new DNA synthesis. In summary, the document provides an overview of DNA damage sources and types as well as the key repair mechanisms cells use to correct DNA damage.
DNA repair mechanisms in prokaryotes involve direct repair, excision repair, and mismatch repair. Direct repair converts damaged nucleotides directly back to their original structure using enzymes like photolyase. Excision repair removes damaged sections of DNA through base excision repair which removes single damaged bases using glycosylases and AP endonucleases, or nucleotide excision repair which removes short oligonucleotides. Mismatch repair recognizes and fixes errors made during DNA replication by distinguishing the parental DNA strands and excising the newly synthesized strand containing mistakes.
Most DNA damage is repaired by two general classes of mechanisms: direct reversal of the chemical reaction that caused the damage, or removal and replacement of damaged bases. The most common types of DNA damage include deamination, depurination, pyrimidine dimers caused by UV light, alkylation by chemicals, and oxidative damage. Specific repair pathways have evolved to fix different types of lesions. Most repair is via excision repair pathways, including base excision repair, nucleotide excision repair, and mismatch repair. Double-strand breaks are repaired by homologous recombination, which uses the intact homologous strand as a template, or non-homologous end joining, which is more error-prone. Recombination pathways
DNA is constantly damaged by cellular metabolism, environmental factors like UV light, and replication errors. To prevent mutations, cells have direct damage reversal and excision repair mechanisms. Direct reversal uses enzymes like photolyases and alkyltransferases to directly restore damaged bases. Excision repair involves removing the damaged segment via pathways like base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). BER repairs single base changes while NER excises oligonucleotides up to 30 bases. MMR corrects errors made during replication. Defects in these pathways are associated with cancers and genetic disorders like xeroderma pigmentosum.
This class recording deals with the sources of DNA damage and the probable repair mechanisms operated within the cell systems. This presentation is prepared in view of students of masters level for updating their knowledge on Molecular Cell Biology.
This document summarizes several DNA repair mechanisms in bacteria:
1. Reversal mechanisms like photoreactivation repair pyrimidine dimers through photolyase enzymes. Excision repair involves removing damaged sections through nuclease cleavage and filling in with DNA polymerase.
2. Mismatch repair recognizes and fixes mispaired bases using methylation patterns to identify the parental strand for correction.
3. Recombination repair retrieves undamaged DNA sequences from a homologous chromosome.
4. Error-prone repair allows replication past lesions by translesion synthesis, often introducing mutations, regulated by umuC and umuD genes during the SOS response.
1. DNA can be damaged through various mechanisms including base substitutions during replication, base changes due to instability, and damage from chemicals and environmental agents.
2. This document describes different types of DNA damage including mismatches, missing or altered bases, single and double strand breaks, and cross-linking.
3. DNA repair mechanisms are discussed, including mismatch repair, removal of incorrect bases by uracil glycosylase, and light-dependent and light-independent repair of thymine dimers through excision and recombinational repair.
1. Experiments in the 1940s-1950s provided evidence that DNA, not protein, is the genetic material. This included Avery, MacLeod and McCarty's experiment showing only DNA could transform bacteria.
2. Further evidence came from Hershey and Chase's experiment labelling bacterial virus DNA and protein differently, finding that DNA entered host bacteria cells while protein did not.
3. DNA can be damaged by various agents like radiation, chemicals, and oxidation. Cells have multiple DNA repair mechanisms like base-excision repair and nucleotide-excision repair to repair damages and prevent mutations.
DNA is constantly damaged by radiation, chemicals, and other agents. There are multiple pathways for repairing DNA damage, including direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. Base excision repair removes individual damaged bases. Nucleotide excision repair removes short fragments of 24-32 bases to repair more substantial damage like thymine dimers. Mismatch repair recognizes and fixes incorrect incorporations during DNA replication. Together, these pathways help maintain the integrity of DNA.
DNA is constantly damaged by radiation, chemicals, and oxidation. Failure to repair DNA damage can lead to mutations. There are two main types of DNA repair - direct reversal and excision repair. Excision repair includes base excision repair, nucleotide excision repair, mismatch repair, and strand break repair. These pathways remove damaged DNA sections and replace them with the correct sequence to prevent mutations. Defects in DNA repair genes increase cancer risk.
The document discusses DNA damage and repair mechanisms in human cells. It begins by explaining how errors can occur during DNA replication and how environmental agents like chemicals and radiation can damage DNA. It then describes different types of DNA damage and several pathways cells use to repair damaged DNA, including direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. It provides details on these repair mechanisms and how they work to recognize and remove damaged sections of DNA before replacing them. The document concludes by discussing some genetic diseases associated with defects in DNA repair systems, like xeroderma pigmentosum, progeria, and Werner syndrome.
Polymerase chain reaction (PCR) is a technique used to amplify specific DNA sequences. It involves cycling between high and low temperatures to separate DNA strands and allow for replication. This allows for targeted amplification of millions of copies of a particular DNA sequence. Real-time quantitative PCR (qPCR) allows for detection and quantification of DNA during amplification through the use of fluorescent probes. Reverse transcription PCR (RT-PCR) first converts RNA to DNA before amplification. PCR techniques like qRT-PCR are currently used for accurate diagnosis of COVID-19 by detecting the SARS-CoV-2 virus from samples.
This document discusses the mating systems of fungi. It begins by defining fungi and describing their general characteristics, such as being eukaryotic and multicellular. It then discusses the four major classes of fungi - Chytridiomycota, Zygomycota, Ascomycota, and Basidiomycota - and describes their life cycles, morphologies, and modes of sexual and asexual reproduction. Deuteromycota, or imperfect fungi, are also introduced as fungi that lack meiotic states and reproduce strictly asexually. In summary, the document provides an overview of fungal taxonomy, characteristics, and reproductive processes.
This document summarizes the mechanisms of DNA repair. It discusses various types of DNA damage including tautomerization, deamination, oxidation, alkylation, and pyrimidine dimers. The main DNA repair mechanisms are damage reversal, damage removal, and damage tolerance. Damage reversal includes photoreactivation and direct repair enzymes. Damage removal consists of base excision repair, nucleotide excision repair, and mismatch repair. Damage tolerance uses error-prone repair or double-strand break repair. Accumulation of unrepaired DNA damage over time contributes to aging.
DNA repair mechanisms identify and correct damage to DNA. There are two main types of DNA damage: endogenous damage caused by metabolic byproducts, and exogenous damage caused by external factors like radiation or toxins. The main DNA repair pathways are direct reversal, base excision repair, nucleotide excision repair, mismatch repair, nonhomologous end joining, and homologous recombination. These pathways utilize various enzymes to recognize damage, cut and remove damaged sections of DNA, and use undamaged DNA as a template for repair synthesis to restore the proper DNA sequence. Defects in certain DNA repair pathways can cause human diseases like xeroderma pigmentosum or Cockayne syndrome.
This document discusses DNA repair mechanisms, specifically nucleotide excision repair. It provides details on:
1) Nucleotide excision repair is a mechanism to repair DNA damage such as thymine dimers caused by UV light. It involves the uvrA, uvrB, uvrC, and uvrD genes which encode proteins that recognize distortions in DNA structure and cut out the damaged region for replacement.
2) If nucleotide excision repair fails, it can result in genetic disorders like xeroderma pigmentosum which increases skin cancer risk, or Cockayne syndrome which involves neurological issues.
The document discusses various types of DNA damage including deamination, depurination, UV light-induced T-T and T-C dimers, alkylation, oxidative damage, replication errors, and double-strand breaks. It then summarizes different DNA repair pathways such as base excision repair, nucleotide excision repair, mismatch repair, direct repair, recombination repair, and non-homologous end-joining. The SOS response in bacteria is also summarized as activating error-prone repair when normal repair pathways are overwhelmed.
DNA repair mechanisms are essential for maintaining genomic integrity. There are several pathways for repairing different types of DNA damage: mismatch repair fixes errors during DNA replication, base excision repair removes damaged bases, nucleotide excision repair replaces larger sections of damaged DNA, and double-strand break repair fixes breaks in both DNA strands. Defects in DNA repair genes can lead to increased cancer risks and genetic disorders like xeroderma pigmentosum and Fanconi anemia. Overall, DNA repair helps prevent mutations from being passed to new cells.
1) The document discusses various agents that can damage DNA like radiation, chemicals, and how the cell repairs this damage through mechanisms like base excision repair, nucleotide excision repair, mismatch repair, and strand break repair.
2) It also discusses several diseases associated with defective DNA repair systems like Xeroderma pigmentosum, Ataxia telangiectasia, Bloom syndrome, Cockayne's syndrome, and Trichothiodystrophy.
3) Each disease is characterized by specific clinical features that result from an inability to properly repair DNA damage.
This document discusses DNA damage and repair mechanisms. It begins by introducing DNA damage and its sources, including endogenous sources like reactive oxygen species and exogenous sources like radiation. It then describes different types of DNA damage such as single base alterations, double base alterations, chain breaks, and cross-linkages. The document proceeds to explain four main DNA repair pathways: photoreactivation, base excision repair, nucleotide excision repair, and mismatch repair. Each repair pathway involves specific enzymes to identify and remove damaged DNA and allow for new DNA synthesis. In summary, the document provides an overview of DNA damage sources and types as well as the key repair mechanisms cells use to correct DNA damage.
DNA repair mechanisms in prokaryotes involve direct repair, excision repair, and mismatch repair. Direct repair converts damaged nucleotides directly back to their original structure using enzymes like photolyase. Excision repair removes damaged sections of DNA through base excision repair which removes single damaged bases using glycosylases and AP endonucleases, or nucleotide excision repair which removes short oligonucleotides. Mismatch repair recognizes and fixes errors made during DNA replication by distinguishing the parental DNA strands and excising the newly synthesized strand containing mistakes.
Most DNA damage is repaired by two general classes of mechanisms: direct reversal of the chemical reaction that caused the damage, or removal and replacement of damaged bases. The most common types of DNA damage include deamination, depurination, pyrimidine dimers caused by UV light, alkylation by chemicals, and oxidative damage. Specific repair pathways have evolved to fix different types of lesions. Most repair is via excision repair pathways, including base excision repair, nucleotide excision repair, and mismatch repair. Double-strand breaks are repaired by homologous recombination, which uses the intact homologous strand as a template, or non-homologous end joining, which is more error-prone. Recombination pathways
DNA is constantly damaged by cellular metabolism, environmental factors like UV light, and replication errors. To prevent mutations, cells have direct damage reversal and excision repair mechanisms. Direct reversal uses enzymes like photolyases and alkyltransferases to directly restore damaged bases. Excision repair involves removing the damaged segment via pathways like base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). BER repairs single base changes while NER excises oligonucleotides up to 30 bases. MMR corrects errors made during replication. Defects in these pathways are associated with cancers and genetic disorders like xeroderma pigmentosum.
This class recording deals with the sources of DNA damage and the probable repair mechanisms operated within the cell systems. This presentation is prepared in view of students of masters level for updating their knowledge on Molecular Cell Biology.
This document summarizes several DNA repair mechanisms in bacteria:
1. Reversal mechanisms like photoreactivation repair pyrimidine dimers through photolyase enzymes. Excision repair involves removing damaged sections through nuclease cleavage and filling in with DNA polymerase.
2. Mismatch repair recognizes and fixes mispaired bases using methylation patterns to identify the parental strand for correction.
3. Recombination repair retrieves undamaged DNA sequences from a homologous chromosome.
4. Error-prone repair allows replication past lesions by translesion synthesis, often introducing mutations, regulated by umuC and umuD genes during the SOS response.
1. DNA can be damaged through various mechanisms including base substitutions during replication, base changes due to instability, and damage from chemicals and environmental agents.
2. This document describes different types of DNA damage including mismatches, missing or altered bases, single and double strand breaks, and cross-linking.
3. DNA repair mechanisms are discussed, including mismatch repair, removal of incorrect bases by uracil glycosylase, and light-dependent and light-independent repair of thymine dimers through excision and recombinational repair.
1. Experiments in the 1940s-1950s provided evidence that DNA, not protein, is the genetic material. This included Avery, MacLeod and McCarty's experiment showing only DNA could transform bacteria.
2. Further evidence came from Hershey and Chase's experiment labelling bacterial virus DNA and protein differently, finding that DNA entered host bacteria cells while protein did not.
3. DNA can be damaged by various agents like radiation, chemicals, and oxidation. Cells have multiple DNA repair mechanisms like base-excision repair and nucleotide-excision repair to repair damages and prevent mutations.
DNA is constantly damaged by radiation, chemicals, and other agents. There are multiple pathways for repairing DNA damage, including direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. Base excision repair removes individual damaged bases. Nucleotide excision repair removes short fragments of 24-32 bases to repair more substantial damage like thymine dimers. Mismatch repair recognizes and fixes incorrect incorporations during DNA replication. Together, these pathways help maintain the integrity of DNA.
DNA is constantly damaged by radiation, chemicals, and oxidation. Failure to repair DNA damage can lead to mutations. There are two main types of DNA repair - direct reversal and excision repair. Excision repair includes base excision repair, nucleotide excision repair, mismatch repair, and strand break repair. These pathways remove damaged DNA sections and replace them with the correct sequence to prevent mutations. Defects in DNA repair genes increase cancer risk.
The document discusses DNA damage and repair mechanisms in human cells. It begins by explaining how errors can occur during DNA replication and how environmental agents like chemicals and radiation can damage DNA. It then describes different types of DNA damage and several pathways cells use to repair damaged DNA, including direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. It provides details on these repair mechanisms and how they work to recognize and remove damaged sections of DNA before replacing them. The document concludes by discussing some genetic diseases associated with defects in DNA repair systems, like xeroderma pigmentosum, progeria, and Werner syndrome.
Polymerase chain reaction (PCR) is a technique used to amplify specific DNA sequences. It involves cycling between high and low temperatures to separate DNA strands and allow for replication. This allows for targeted amplification of millions of copies of a particular DNA sequence. Real-time quantitative PCR (qPCR) allows for detection and quantification of DNA during amplification through the use of fluorescent probes. Reverse transcription PCR (RT-PCR) first converts RNA to DNA before amplification. PCR techniques like qRT-PCR are currently used for accurate diagnosis of COVID-19 by detecting the SARS-CoV-2 virus from samples.
This document discusses the mating systems of fungi. It begins by defining fungi and describing their general characteristics, such as being eukaryotic and multicellular. It then discusses the four major classes of fungi - Chytridiomycota, Zygomycota, Ascomycota, and Basidiomycota - and describes their life cycles, morphologies, and modes of sexual and asexual reproduction. Deuteromycota, or imperfect fungi, are also introduced as fungi that lack meiotic states and reproduce strictly asexually. In summary, the document provides an overview of fungal taxonomy, characteristics, and reproductive processes.
Biofilms are complex communities of microorganisms encased in a self-produced matrix that form on living and non-living surfaces. They are the primary mode of existence for bacteria in aqueous environments. The establishment and maintenance of biofilms is a highly organized, multi-step process involving initial attachment, growth, production of extracellular matrix, and potential later attachment of additional species. Biofilms provide advantages to microorganisms like enhanced nutrient uptake, protection, and social coordination between cells.
This document discusses strategies and techniques for identifying human disease genes through gene mapping and positional cloning. It provides an overview of the human genome project and approaches to physical and genetic mapping. It also describes key methods used in positional cloning, including genetic mapping, linkage analysis, identifying candidate genes, and testing for mutations in affected individuals.
Sickle cell anemia is caused by a mutation in the beta-globin gene on chromosome 11. This mutation results in abnormal hemoglobin called hemoglobin S. Hemoglobin S polymerizes and causes red blood cells to take on a sickle shape under conditions of low oxygen. Symptoms of sickle cell anemia include anemia, pain crises, infections, and organ damage. Treatments include medications to reduce pain and prevent complications, blood transfusions, antibiotics to prevent infection, and potentially a stem cell transplant for severe cases.
Microbiology techniques allow scientists to culture, examine, and identify microorganisms. There are five basic techniques: inoculation introduces a microbe sample into nutrient medium, incubation encourages growth, isolation separates individual species, inspection examines cultures visually, and identification determines the microbe. Microscopes are important tools, with brightfield, darkfield, phase contrast, fluorescence, confocal, transmission electron, and scanning electron variations. Staining techniques like Gram staining and acid-fast staining reveal cell structures and aid identification.
Microscopy is the use of microscopes to view objects that are too small to be seen by the naked eye. There are several types of microscopes that use different technologies including optical/light microscopy, electron microscopy, and scanning probe microscopy. Optical microscopy uses lenses and light to magnify specimens, but is limited by the wavelength of visible light. More advanced microscopes like electron microscopes use electron beams instead of light for higher resolution. Microscopy has advanced significantly over time from early basic lenses to today's high resolution technologies.
The document summarizes key aspects of DNA replication in bacteria. It describes how the leading strand is synthesized continuously in the 5' to 3' direction, while the lagging strand is synthesized discontinuously in short Okazaki fragments in the 3' to 5' direction. It also discusses the roles of the helicase, which unwinds the DNA, and the single-stranded binding protein, which coats and protects the exposed single strands. Primers are also required to provide 3' OH ends for DNA polymerase to begin synthesizing new DNA strands. Coordination is needed between synthesis of the leading and lagging strands at the replication fork.
This document provides an overview of RNA editing. It begins by defining RNA editing as any process that results in a change to an RNA transcript sequence compared to the DNA template, excluding splicing. It then discusses the two main types of editing - base modification and insertion/deletion. Key points include that editing occurs in the nucleus, mitochondria and chloroplasts; the mechanism of A-to-I editing involves adenosine being deaminated to inosine; and editing is directed by guide RNAs in kinetoplastids. The document also summarizes a case study on the role of the SLO2 gene in plant stress responses.
The document summarizes regulation of DNA replication in eukaryotes. It explains that eukaryotic genomes are divided into replicons that are each activated once per cell cycle. This is achieved through licensing factors that load onto origins of replication in G1 phase, but are removed or inactivated during DNA replication, preventing re-replication. The key licensing factors are the origin recognition complex (ORC) and proteins Cdc6 and Cdt1, which load the MCM complex onto DNA.
The document summarizes the organization of the human genome and genes. It discusses the general organization of the human genome including nuclear and mitochondrial genomes. It describes gene distribution and density in the nuclear genome. It provides details on the organization of different types of genes such as rRNA, mRNA, small nuclear RNA genes, overlapping genes, and multi-gene families. It also discusses various repetitive elements in the genome including SINEs, LINEs, microsatellites, and minisatellites. Finally, it covers topics like chromatin structure, histones, heterochromatin, euchromatin, and X-inactivation.
The document discusses the production of penicillin from Penicillium chrysogenum fungi. Key points:
- Penicillin is produced through a fed-batch fermentation using P. chrysogenum, which secretes penicillin into the medium using lactose and yeast extract as carbon and nitrogen sources.
- Downstream processing involves filtration to remove cells, extraction of penicillin from the filtrate using butylacetate counter-current, and precipitation of purified penicillin using potassium salts.
- Genetic modification has improved penicillin yields from 1 mg/dm3 originally to over 50 g/dm3 currently using P. chrysogenum.
This document discusses various patterns of inheritance including Mendelian patterns like autosomal dominant, autosomal recessive, X-linked, and Y-linked inheritance. It also covers non-Mendelian inheritance patterns such as mitochondrial, genomic imprinting, unstable repeat expansions, uniparental disomy, mosaicism, and multigenic inheritance. For each pattern of inheritance, the key features are defined.
Microbiology is the study of microorganisms that require magnification to be seen clearly, such as viruses, bacteria, fungi, algae, and protozoa. Some key developments in the history of microbiology include Robert Hooke discovering cells in 1665, Anton van Leeuwenhoek first observing microbes in 1674, Louis Pasteur disproving spontaneous generation and germ theory of disease in 1861, Robert Koch establishing methods to prove microbes cause specific diseases in 1876, and Alexander Fleming discovering the first antibiotic, penicillin, in 1928.
Epigenetics involves changes in gene expression without altering the DNA sequence. There are three main types of epigenetic modifications: DNA methylation, histone modification, and microRNAs. DNA methylation involves the addition of methyl groups to cytosine bases by DNMT enzymes and regulates gene expression. Histone modification involves changes like acetylation and methylation that affect chromatin structure and accessibility of DNA. MicroRNAs are short non-coding RNAs that regulate gene expression post-transcriptionally by inhibiting mRNA. Together, these epigenetic mechanisms regulate processes like cell differentiation through controlling gene activity.
1. Gas chromatography and liquid chromatography techniques such as HPLC are commonly used to characterize and study protein pharmaceuticals. HPLC methods like reverse phase HPLC can separate proteins based on hydrophobic interactions.
2. Other analytical techniques used include spectroscopy, electrophoresis, and mass spectrometry which provide information on protein structure, purity, quantity and degradation.
3. The selection of technique depends on the desired information and factors like resolution, sensitivity, sample requirements and throughput. Together these analytical approaches support protein quality control and characterization.
The document discusses DNA replication in prokaryotes and eukaryotes. It explains that replication involves initiation at an origin of replication, followed by unwinding of the DNA double helix by helicase. RNA primers are synthesized by primase and DNA polymerase adds nucleotides to the primers to elongate DNA strands. In prokaryotes, leading and lagging strands are synthesized continuously and discontinuously respectively to form Okazaki fragments. Enzymes like DNA polymerase, ligase, and topoisomerase ensure high fidelity and processivity of replication. Telomerase maintains telomere integrity in eukaryotes during DNA replication.
1) The document discusses the history and evolution of microbiology from its early pioneers like Leeuwenhoek and Pasteur to modern classification.
2) It highlights key discoveries such as Leeuwenhoek first observing microorganisms under a microscope. Pasteur later debunked spontaneous generation and established germ theory of disease.
3) Koch further advanced the field with techniques like staining and culturing bacteria, and formulated Koch's postulates for linking microbes to disease. This helped establish microbiology as a science.
This document provides an overview of Mendelian genetics principles including:
- Mendel studied trait transmission in pea plants and described foundational genetic principles.
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1. Mechanisms of DNA Damage and
Repair
Dr. Nasreen S. Munshi
Assistant Professor,
Institute of Science,
Nirma University,
Ahmedabad.
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26.
27.
28. Mechanisms of DNA Damage and
Repair
Dr. Nasreen S. Munshi
Assistant Professor,
Institute of Science,
Nirma University,
Ahmedabad.
29. Biological indications of damage to DNA
- Radiations or chemicals
- Bacteria lose the ability to develop colonies
- Phages lose the plaques-forming ability
- Survival curve: dose-response graph: plot of initial
population that survives the doses of radiation/chemical
vs. some measures of exposure
30.
31. Damages caused by radiations:
(1) Single strand breaks are for the most part are resealed by
DNA ligase and do not contribute to lethality.
(2) Double strand breaks are often lethal because the free ends
initiate degradation of the DNA by nucleases.
(3) Damage to bases, which is an oxidative process requiring
oxygen molecule, is often lethal probably because the
damaged bases constitute a replication block.
Ultraviolet Radiation:
T7 DNA = 25 X 106
Lambda DNA = 31 X 106
T5 DNA = 76 X 106
32. T7 DNA = 25 X 106
Lambda DNA = 31 X 106
T5 DNA = 76 X 106
34. (1) The dimer can be directly repaired by photoreactivation
(2) The dimer can be excised and correct bases replaced by
DNA polymerase I
(3) DNA synthesis can reinitiate on the other side of dimer
and then the dimer can be repaired by recombination repair
mechanism
(4) Induction of SOS repair can allow trans-dimer synthesis
(error prone repair)
35.
36. Organisms also possess systems that enable
them to replicate damaged regions of their
genome without prior repair – Homologous
Recombination based systems
37.
38.
39.
40.
41. [I] Direct repair systems fill in nicks and correct some types of
nucleotide modification:
- Most of the DNA damages are repaired by excision of damaged nucleotide
followed by resynthesis of a new stretch of DNA.
- A few types can be repaired directly
(i) Nicks can be repaired by
DNA ligase, where
phosphodiester bond has
been broken
- Nicks are produced by
ionizing radiations.
42. (ii) Alkylation damages are directly repaired reversibly by repair enzymes that
transfer the alkyl group from the nucleotide to their own polypeptide chains.
- E. coli possesses Ada enzyme: involved in adaptive process that removes alkyl
groups attached to O-groups at positions 4 and 6 of thymine and guanine
respectively.
- Ada can also repair phosphodiester bonds that have been methylated.
(iii) Cyclobutyl dimers are repaired by a light dependent direct system called
photoreactivation.
- DNA photolyase: stimulated by light (300 – 500 nm)
- Binds to cyclobutyl dimers and converts them back to the original monomeric
nucleotides.
- Not universal mechanism, in most bacteria, many eukaryotes but not in humans
and mammals.
43. [II] Excision Repair:
- Pathway: includes many components
(a) Base Excision Repair
- removal of damaged nucleotide base, creating an AP site
- Excision of a short piece of polynucleotide around AP site
- Resynthesis with DNA polymerase and ligation
(b) Nucleotide Excision Repair
- similar but does not remove the damaged nucleotide base
- Excision of a short piece of polynucleotide around damaged site
- Resynthesis with DNA polymerase and ligation
- Can repair severely damaged areas of DNA
44. (a) Base Excision Repair
- least complex
- repairs the bases which suffer minor damages.
- e.g. by alkylating agents
→ initiated by DNA glycosylases: cleaves -N-glycosidic
bond between a damaged base and the sugar component of
nucleotide.
45.
46. Glycosylases are specific for specific bases :
(i) Deaminated bases: Uracil (i.e deaminated C)
Hypoxanthine (i.e. deaminated A)
(ii) Oxidation products: 5-hydroxy C and thymine glycol
(iii) Methylated bases: 3-methyl A, 7-methyl G & 2-methyl C
Other DNA glycosylases remove normal bases as part of mismatch
repair system.
Mechanism:
→Removes the damaged base by “flipping” the structure to a
position outside the helix and then detaching it from
polynucleotide
→ Thus create an AP site (baseless site)
→ create a single nucleotide gap in second step
48. - The second step
❖ AP endonuclease
(exonuclease III or endonuclease
IV), which cut the phosphodiester
bond on 5’ side of AP site.
❖ some AP endonuclease can also
remove sugar while others require
help of phosphodiesterase
❖ Alternatively, some DNA
glycosylases, themselves make a
cut at 3’ side of AP site when it
removes damaged base; next
sugar is removed by
phosphodiesterase
The resulting gap is filled by
DNA polymerase I in E. coli
DNA Pol : Mammals
DNA Pol : Yeast
49.
50. [b] Nucleotide Excision Repair
It can repair extensive type of damages, such as cross links and
attachment of large chemical groups.
It can also repair cyclobutyl dimers by a Dark Repair Process.
Difference with Base Excision:
(i) It is not preceded by removal of selective base
(ii) A longer stretch of polynucleotide is removed.
Two types is E. coli
• “Short Patch” process: 12 nucleotides long
• “Long Patch” process: up to 2 kb
51. (i) “Short Patch” process:
- Initiated by UvrABC endonuclease, a
multienzyme complex
- Trimer: 2 Uvr A + 1 Uvr B proteins
- How site is recognized is not known
- General features such as distortion
- Uvr A must be involved in recognition, as it
leaves as soon as site is located.
- Followed by binding of Uvr C
- 1st cut is made by Uvr B at 5th
phosphodiester bond downstream of the
damaged site
- 2nd cut by Uvr C at 8th phosphodiester bond
upstream of damage site = resulting in 12
nucleotide excision
- Excised segment → removed by DNA
helicase II
- Uvr C also detaches
- Uvr B remains attached
52. Role of Uvr B protein after excision: (remains bound to single
stranded DNA)
• It prevents base pairing with itself
• Prevents damage to single strand
• Directs DNA polymerase to the site which needs to be repaired
(ii) “Long patch” nucleotide excision repair system:
- Involves Uvr proteins
- Less well studied
- Works with extensive damage
- In Eukaryotes, nucleotide excision repair is termed as “long
patch” → removes only 24-29 nucleotides of DNA
- There is no short patch system in Eukaryotes
- Enzyme systems are all different, in humans at least 16 proteins
are involved.
- Downstream cut is made at same position, but with a more
distant upstream cut.
53.
54. - DNA around the damage site is melted by a helicase.
- Because the endonucleases cut ssDNA at junction with a double
stranded region.
- In this activity TFIIH is involved.
- It is also one of the components of RNA polymerase II -initiation
complex.
- Initial assumption: TFIIH: 2 roles – one in transcription, one in
repair
- Direct link was discovered by discovery of a new repair system:
“Transcription-coupled repair”.
- This system repairs damages in strands of genes that are actively
transcribed.
- Hence, Transcription-coupled repair is a modified version of
nucleotide excision repair.
55. [III] Mismatch Repair
- Mainly for correcting error of replication.
- Earlier discussed methods search for abnormal chemical
structures, but can not identify mismatch.
- As it is normal nucleotide, A, T, C or G.
- This repair system looks for absence of base pairing between
parent and daughter strands.
- Then it excises part of daughter polynucleotide and fills in gap.
- Important: repair must be there in newly synthesized strand
which has acquired mismatch and parent has correct sequence.
- How is it identified?
56.
57. After replication, DNA is methylated at
5’-GATC-3’ : ‘A’ converted to ‘6-methyladenine’
: DNA adenine methylase (Dam)
5’-CCAGG-3’ and 5’-CCTGG-3’
: ‘C’ converted to ‘5-methylcytosine’
: DNA cytosine methylase (Dcm)
Daughter strand is different from parent strand as it is initially
under - methylated.
Parent polynucleotide has full complement of methyl groups,
hence the two can be distinguished.
These modifications are not mutagenic, as base pairing
specificity is not altered.
58.
59.
60. E. coli has three mismatch repair systems:
(1) “Long patch”
(2) “Short patch”
(3) “Very short patch”
61. (1) Long Patch System: Replaces a kilobase or more of DNA
: Requires activities of Mut S, Mut H and
Mut L proteins
: Requires DNA helicase II (same as in
nucleotide excision repair)
Mut S protein : Recognizes mismatch (absence of H
bonds)
Mut H protein : Distinguishes two strands by binding to
unmethylated 5’-GATC-3’ sequence
Mut L protein : Role not clear
supposed to help binding of Mut H in
vicinity of mismatch identified by Mut S
62. - After binding, Mut H cuts
phosphodiester bonds
immediately upstream of G (in
unmethylated 5’-GATC-3’
recognition site)
- DNA helicase II detaches
single strand.
- No cut downstream
- Detached single stranded
region is degraded by an
exonuclease which follows
helicase.
- Gap is filled in by DNA Pol I
and DNA ligase.
65. MutS forms a dimer (MutS2) and binds the mutated DNA.
MutH binds at hemimethylated sites along the daughter DNA, but its
action is activated only upon contact by a MutL dimer (MutL2), which
binds the MutS-DNA complex and acts as a mediator between MutS2 and
MutH, activating the latter.
The DNA is looped out to search for the nearest d(GATC) methylation site
to the mismatch, which could be up to 1 kb away.
Upon activation by the MutS-DNA complex, MutH nicks the daughter
strand near the hemimethylated site. MutL recruits UvrD helicase (DNA
Helicase II) to separate the two strands.
The entire MutSHL complex then slides along the DNA in the direction of
the mismatch, liberating the strand to be excised as it goes.
An exonuclease trails the complex and digests the ss-DNA tail. The
exonuclease recruited is dependent on which side of the mismatch MutH
incises the strand – 5' or 3'. If the nick made by MutH is on the 5' end of
the mismatch, either RecJ or ExoVII (both 5' to 3' exonucleases) is used.
If, however, the nick is on the 3' end of the mismatch, ExoI (a 3' to 5'
enzyme) is used.
66. (b) Short Patch Repair:
- Proteins recognizing mismatch are different.
- Excision of less than 10 nucleotides
- Mut Y recognizes A-G or A-C mismatches
(c) Very Short Patch Repair
- Recognizes and corrects G-T mismatches
- Recognized by Vsr endonuclease
67. [IV] Repair of DNA Breaks:
* Single Strand Break Repair
- produced by some type of oxidative damage
- exposed single strand is coated with PARP1 proteins, which
protects it from breaking and taking part in unwanted
recombination.
- Break is filled by enzymes involved in excision repair
pathways.
69. - More serious type of damage
- Generated by exposure to ionizing radiation
- Two ways to repair: (i) involving homologous recombination
(ii) nonhomologous end-joining (NHEJ)
- NHEJ – By studies on mutant human cell lines, various sets of
genes are involved
- These genes specify a multicomponent protein complex which
directs DNA ligase to the break.
* Double Strand Break Repair
70. * Double Strand Break Repair
The complex includes two copies of Ku
protein, each copy binds to broken end.
Individual Ku proteins have high affinity for
each other.
Two ends of DNA brought into proximity.
Ku – DNA - PKCS protein kinase →
activates a third protein XRCC4 → interacts
with mammalian DNA ligase IV for
directing it to double strand break
Bacterial homologs of mammalian Ku
proteins have been found, which act in
conjunction with bacterial ligases –
simplified version.
71.
72. [V] BYPASSING DNA DAMAGE DURING GENOME
REPLICATION
- Extensive damage cell faces a tough choice between dying or
attempting to replicate the damaged region though it is error-
prone causing mutations.
- Uses one of the emergency procedures
* SOS Response:
- Best studied process
- Enables cell to replicate DNA even if AP sites/ cyclobutyl dimers/
other photoproducts are present.
- Mutasome (DNA Pol V) : A trimer - UmuD’2C : 2 UmuD’ &
1 UmuC and several copies of Rec A proteins
- Rec A protein - single strand binding protein – role in repair and
recombination pathways
- Rec A binding enables mutasome to replace DNA Pol III, carries
out replication until damaged site is bypassed → DNA Pol III
takes over.
74. - Rec A is activator of SOS response
- This protein is activated by unknown chemical signals that
indicate presence of extensive DNA damage
- Rec A cleaves a number of target proteins
(i) UmuD → UmuD’
(ii) Repressor Lex A → switches on expression of no. of genes
(involved in repair processes) repressed by Lex A
(iii) Lex A also is a repressor of rec A gene : its cleavage results
in 50 fold production of Rec A protein.
(iv) cI repressor of phage → any integrated prophage is there
→ it can excise and leave
75. Cell pays a price – high rate of mutations
Mutasome does not repair – damaged portion of polynucleotide is
replicated
Random selection of nucleotides; but mostly ‘A’ opposite AP site
Also assumed to create high mutation rate – advantageous (?)
Other than SOS : 2 other E. coli polymerases act in similar way.
DNA Pol II can bypass nucleotides bound to mutagenic chemicals
such as N-2-acetylaminofluorene and
DNA Pol IV (also called Din B): can replicate through a region of
template DNA in which two parent polynucleotides are misaligned.
Bypass polymerases also in eukaryotes :
DNA Pol & : bypass cyclobutyl dimers
DNA Pol and : replicate through photoproducts & AP sites.
Defects: E.g. Xeroderma pigmentosum (Nucleotide Excision repair is
defective which is the only means to repair T-T dimer) – person is
hypersensitive to UV – Skin cancer.
https://www.youtube.com/watch?v=31stiofJjYw
76. Useful videos to understand DNA damage repair mechanisms:
1. Nucleotide Excision Repair
https://youtu.be/HABw8T_qYjQ (a simplified version)
https://youtu.be/94ou07-qMSg
Eukaryotic Nucleotide Excision Repair:
https://youtu.be/o-qMG6ffxUU
2. Mismatch Repair:
https://youtu.be/p3MXIKWAi2w
https://youtu.be/dgPh1qigv7s
3. NHEJ Mechanism: Double Strand Break Repair
https://www.youtube.com/watch?v=31stiofJjYw
https://youtu.be/SfAWyF3WabE
https://youtu.be/rkQk9vWtB6k
https://youtu.be/7DkIBYIqIgQ
4. SOS Response:
Activation of SOS Response: https://youtu.be/MTcPFRZLLxc
SOS Response: https://youtu.be/MmwP9YzEXK0
77. 5. Photoreactivation Mechanism
https://youtu.be/CwuXOmtl_zI
6. Alkylation damage repair
https://youtu.be/4QoJyn-rSHg
7. Base Excision Repair
Simplified version: https://youtu.be/Pw6P6sCcjpM
https://youtu.be/JV7onc5Ja1c
Note: Pay attention to mechanisms of repair, there might be slight variations
in the overall repair process depicted in different videos. For details, refer to
text material shared.