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.
DNA can be damaged through various means, including single base alterations, double base alterations, chain breaks, and cross-linking. Single base alterations include depurination, deamination, alkylation, base analogue incorporation, and mismatch bases. Double base alterations include pyrimidine dimers and purine dimers caused by UV radiation. Chain breaks include single and double stranded breaks caused by irradiation and free radicals. Cross-linking can occur between DNA and DNA or DNA and proteins due to UV radiation, ionizing radiation, and free radicals. Unrepaired damage can lead to mutations if incorrectly repaired during replication.
DNA repair mechanisms identify and correct damage to DNA that occurs due to normal cellular processes and environmental factors. There are two main types of DNA damage: endogenous damage caused by normal cellular processes and exogenous damage caused by external agents like UV radiation and chemicals. The main repair mechanisms are base excision repair, nucleotide excision repair, direct repair via photolyases, and error-prone repair systems like SOS repair. Together, these pathways maintain genome integrity by repairing different types of DNA lesions.
1. DNA is constantly exposed to damage from the environment and errors during replication. Cells have several DNA damage repair mechanisms to fix alterations to maintain genome integrity.
2. The main repair pathways are direct reversal, excision repair including nucleotide excision repair and base excision repair, and mismatch repair which fixes errors made during replication.
3. If damage evades these pathways, error-prone translesion synthesis can occur which often introduces mutations, acting as a last resort to allow replication past lesions.
This document summarizes different types of DNA repair mechanisms including base excision repair, nucleotide excision repair, and their mechanisms in E. coli and humans. It also discusses short patch and long patch base excision repair, and conditions like xeroderma pigmentosum that arise from defects in nucleotide excision repair.
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.
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.
DNA can be damaged through various means, including single base alterations, double base alterations, chain breaks, and cross-linking. Single base alterations include depurination, deamination, alkylation, base analogue incorporation, and mismatch bases. Double base alterations include pyrimidine dimers and purine dimers caused by UV radiation. Chain breaks include single and double stranded breaks caused by irradiation and free radicals. Cross-linking can occur between DNA and DNA or DNA and proteins due to UV radiation, ionizing radiation, and free radicals. Unrepaired damage can lead to mutations if incorrectly repaired during replication.
DNA repair mechanisms identify and correct damage to DNA that occurs due to normal cellular processes and environmental factors. There are two main types of DNA damage: endogenous damage caused by normal cellular processes and exogenous damage caused by external agents like UV radiation and chemicals. The main repair mechanisms are base excision repair, nucleotide excision repair, direct repair via photolyases, and error-prone repair systems like SOS repair. Together, these pathways maintain genome integrity by repairing different types of DNA lesions.
1. DNA is constantly exposed to damage from the environment and errors during replication. Cells have several DNA damage repair mechanisms to fix alterations to maintain genome integrity.
2. The main repair pathways are direct reversal, excision repair including nucleotide excision repair and base excision repair, and mismatch repair which fixes errors made during replication.
3. If damage evades these pathways, error-prone translesion synthesis can occur which often introduces mutations, acting as a last resort to allow replication past lesions.
This document summarizes different types of DNA repair mechanisms including base excision repair, nucleotide excision repair, and their mechanisms in E. coli and humans. It also discusses short patch and long patch base excision repair, and conditions like xeroderma pigmentosum that arise from defects in nucleotide excision repair.
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.
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.
Mitochondrial DNA is circular DNA located in the mitochondria of cells. It is 16kb in size and encodes 37 genes. Mitochondrial DNA is only inherited from the mother and differs from nuclear DNA in several key ways, such as being maternally inherited only. Mutations in mitochondrial DNA can cause diseases often involving the central nervous system or musculoskeletal system. The high mutation rate of mitochondrial DNA is due to lack of protective histones and DNA repair mechanisms.
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.
This document discusses the organization of chromatin and DNA packaging in the cell nucleus. It describes four main levels of chromatin organization: 1) DNA wraps around histone proteins to form nucleosomes, the basic unit of chromatin, 2) Nucleosomes further organize into 30nm fibers, 3) The 30nm fibers then organize into looped domains, and 4) During cell division, the loops compact into mitotic chromosomes. Nucleosomes consist of about 150 base pairs of DNA wrapped around an octamer of core histone proteins, and act to tightly package DNA inside the nucleus.
This document discusses chloroplast DNA (cpDNA). Chloroplasts contain their own circular genome of double-stranded DNA ranging from 140-200kb. The cpDNA contains genes that code for proteins involved in photosynthesis as well as rRNA and tRNA. It has a quadripartite structure containing single copy and inverted repeat regions. Tobacco and liverwort were two of the first chloroplast genomes to be sequenced. Molecular studies of cpDNA regions have been useful for plant systematics. Replication of cpDNA is independent of nuclear DNA and involves enzymes like DNA polymerase and helicase.
Prokaryotic genomes are typically organized as single circular chromosomes that are condensed into a nucleoid region within the cell. DNA supercoiling, which involves the over- or under-winding of DNA strands, facilitates compaction of prokaryotic genomes and enables DNA metabolism. Topoisomerases regulate DNA supercoiling by introducing temporary breaks in DNA strands, allowing strands to pass through one another and relieve torsional stress that builds during processes like transcription and replication. The two major types of topoisomerase are types I and II, which introduce single-strand or double-strand breaks, respectively, in regulating supercoiling levels.
What is Genome,Genome mapping,types of Genome mapping,linkage or genetic mapping,Physical mapping,Somatic cell hybridization
Radiation hybridization ,Fish( =fluorescence in - situ hybridization),Types of probes for FISH,applications,Molecular markers,Rflp(= Restriction fragment length polymorphism),RFLPs may have the following Applications;Advantages of rflp,disAdvantages of rflp, Rapd(=Random amplification of polymorphic DNA),Process of rapd, Difference between rflp &rapd
Co and post translationational modification of proteinsSukirti Vedula
This document discusses co-translational and post-translational modifications of proteins. It begins with an introduction to protein modification and defines co-translational and post-translational modifications. It then covers various co-translational modifications including regulation of translation, protein folding, and enzymes that catalyze protein folding. Post-translational modifications discussed include protein cleavage, glycosylation, addition of GPI anchors, ubiquitination, and phosphorylation. The document provides examples and details for many of the modification processes.
DNA can be damaged by physical, chemical, and environmental agents through various types of alterations including single or double base changes, breaks in the DNA chain, or cross-linkages between bases. The cell has multiple DNA repair mechanisms to correct damage including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. Base excision repair removes single damaged bases while nucleotide excision repair removes larger segments of damaged DNA. Mismatch repair corrects errors that occur during DNA replication. Double-strand break repair repairs more severe breaks in both strands of the DNA that can lead to chromosomal abnormalities. Defects in DNA repair pathways can result in increased cancer risks.
The document discusses DNA denaturation and renaturation, including:
- Denaturation involves unwinding the DNA double helix into single strands through heating or chemical treatment, disrupting hydrogen bonds between base pairs. This increases UV absorption.
- Renaturation is the spontaneous rewinding of single strands back into the original double helix structure when denaturing conditions are removed, through base pairing of complementary strands.
- C0t curves plot the fraction of single strands renatured versus the product of DNA concentration and time, and can indicate the complexity and size of the original DNA sample based on renaturation rates. More complex DNA with more dissimilar sequences takes longer to renature
Dna supercoiling and role of topoisomerasesYashwanth B S
supercoiling is one of the important process to condenses the huge amount of DNA to fit inside the histone and its also plays a role during the replication ,transcription etc..,these activities is carried out by an enzyme called topoisomerases.
This document summarizes homologous recombination in eukaryotes and bacteria. In eukaryotes, homologous recombination repairs double-strand DNA breaks through either the double-strand break repair (DSBR) pathway or synthesis-dependent strand annealing (SDSA) pathway. The DSBR pathway forms double Holliday junctions that are resolved to result in crossover or non-crossover products. In bacteria, the RecBCD pathway repairs double-strand breaks and the RecF pathway repairs single-strand gaps. Both pathways involve strand invasion and branch migration to facilitate homologous recombination.
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.
Mismatch Repair Mechanism Is One Of The Important DNA Repair Mechanism Which Recognizes And Replaces The Wrong Nucleotides. DNA Repair Is Important Since Its Failure Leads To Deadly Diseases Like Cancer. In This Presentation, You Will Learn About DNA Repair, Mismatch Repair, Proteins Involved In Prokaryotic And Eukaryotic MMR, Diagrams, Biological Importance Of MMR And References For Further Study.
This document describes the process of DNA replication in eukaryotes. It occurs in S phase of the cell cycle and involves three main stages: initiation, formation of the initiation complex, and elongation. Initiation requires the assembly of pre-replication complexes containing ORC, Cdc6, Cdt1 and MCM proteins. In S phase, Cdc45 and GINS are recruited to form the initiation complex. Elongation proceeds bidirectionally from replication forks, with leading strand synthesis continuous and lagging strand discontinuous via Okazaki fragments. Replication terminates at telomeres.
E. coli RNA polymerase is an enzyme that catalyzes the formation of phosphodiester bonds between nucleotides during transcription. It is composed of five subunits - two α subunits, one β subunit, one β' subunit, and one ω subunit. Together with a sigma factor, these subunits form the holoenzyme which is required for transcription initiation by binding to promoter sequences on DNA. The sigma factor recognizes specific promoter sequences and directs the holoenzyme to begin RNA synthesis. E. coli has multiple sigma factors that direct transcription of different genes depending on environmental conditions.
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 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.
Mitochondrial DNA is circular DNA located in the mitochondria of cells. It is 16kb in size and encodes 37 genes. Mitochondrial DNA is only inherited from the mother and differs from nuclear DNA in several key ways, such as being maternally inherited only. Mutations in mitochondrial DNA can cause diseases often involving the central nervous system or musculoskeletal system. The high mutation rate of mitochondrial DNA is due to lack of protective histones and DNA repair mechanisms.
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.
This document discusses the organization of chromatin and DNA packaging in the cell nucleus. It describes four main levels of chromatin organization: 1) DNA wraps around histone proteins to form nucleosomes, the basic unit of chromatin, 2) Nucleosomes further organize into 30nm fibers, 3) The 30nm fibers then organize into looped domains, and 4) During cell division, the loops compact into mitotic chromosomes. Nucleosomes consist of about 150 base pairs of DNA wrapped around an octamer of core histone proteins, and act to tightly package DNA inside the nucleus.
This document discusses chloroplast DNA (cpDNA). Chloroplasts contain their own circular genome of double-stranded DNA ranging from 140-200kb. The cpDNA contains genes that code for proteins involved in photosynthesis as well as rRNA and tRNA. It has a quadripartite structure containing single copy and inverted repeat regions. Tobacco and liverwort were two of the first chloroplast genomes to be sequenced. Molecular studies of cpDNA regions have been useful for plant systematics. Replication of cpDNA is independent of nuclear DNA and involves enzymes like DNA polymerase and helicase.
Prokaryotic genomes are typically organized as single circular chromosomes that are condensed into a nucleoid region within the cell. DNA supercoiling, which involves the over- or under-winding of DNA strands, facilitates compaction of prokaryotic genomes and enables DNA metabolism. Topoisomerases regulate DNA supercoiling by introducing temporary breaks in DNA strands, allowing strands to pass through one another and relieve torsional stress that builds during processes like transcription and replication. The two major types of topoisomerase are types I and II, which introduce single-strand or double-strand breaks, respectively, in regulating supercoiling levels.
What is Genome,Genome mapping,types of Genome mapping,linkage or genetic mapping,Physical mapping,Somatic cell hybridization
Radiation hybridization ,Fish( =fluorescence in - situ hybridization),Types of probes for FISH,applications,Molecular markers,Rflp(= Restriction fragment length polymorphism),RFLPs may have the following Applications;Advantages of rflp,disAdvantages of rflp, Rapd(=Random amplification of polymorphic DNA),Process of rapd, Difference between rflp &rapd
Co and post translationational modification of proteinsSukirti Vedula
This document discusses co-translational and post-translational modifications of proteins. It begins with an introduction to protein modification and defines co-translational and post-translational modifications. It then covers various co-translational modifications including regulation of translation, protein folding, and enzymes that catalyze protein folding. Post-translational modifications discussed include protein cleavage, glycosylation, addition of GPI anchors, ubiquitination, and phosphorylation. The document provides examples and details for many of the modification processes.
DNA can be damaged by physical, chemical, and environmental agents through various types of alterations including single or double base changes, breaks in the DNA chain, or cross-linkages between bases. The cell has multiple DNA repair mechanisms to correct damage including base excision repair, nucleotide excision repair, mismatch repair, and double-strand break repair. Base excision repair removes single damaged bases while nucleotide excision repair removes larger segments of damaged DNA. Mismatch repair corrects errors that occur during DNA replication. Double-strand break repair repairs more severe breaks in both strands of the DNA that can lead to chromosomal abnormalities. Defects in DNA repair pathways can result in increased cancer risks.
The document discusses DNA denaturation and renaturation, including:
- Denaturation involves unwinding the DNA double helix into single strands through heating or chemical treatment, disrupting hydrogen bonds between base pairs. This increases UV absorption.
- Renaturation is the spontaneous rewinding of single strands back into the original double helix structure when denaturing conditions are removed, through base pairing of complementary strands.
- C0t curves plot the fraction of single strands renatured versus the product of DNA concentration and time, and can indicate the complexity and size of the original DNA sample based on renaturation rates. More complex DNA with more dissimilar sequences takes longer to renature
Dna supercoiling and role of topoisomerasesYashwanth B S
supercoiling is one of the important process to condenses the huge amount of DNA to fit inside the histone and its also plays a role during the replication ,transcription etc..,these activities is carried out by an enzyme called topoisomerases.
This document summarizes homologous recombination in eukaryotes and bacteria. In eukaryotes, homologous recombination repairs double-strand DNA breaks through either the double-strand break repair (DSBR) pathway or synthesis-dependent strand annealing (SDSA) pathway. The DSBR pathway forms double Holliday junctions that are resolved to result in crossover or non-crossover products. In bacteria, the RecBCD pathway repairs double-strand breaks and the RecF pathway repairs single-strand gaps. Both pathways involve strand invasion and branch migration to facilitate homologous recombination.
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.
Mismatch Repair Mechanism Is One Of The Important DNA Repair Mechanism Which Recognizes And Replaces The Wrong Nucleotides. DNA Repair Is Important Since Its Failure Leads To Deadly Diseases Like Cancer. In This Presentation, You Will Learn About DNA Repair, Mismatch Repair, Proteins Involved In Prokaryotic And Eukaryotic MMR, Diagrams, Biological Importance Of MMR And References For Further Study.
This document describes the process of DNA replication in eukaryotes. It occurs in S phase of the cell cycle and involves three main stages: initiation, formation of the initiation complex, and elongation. Initiation requires the assembly of pre-replication complexes containing ORC, Cdc6, Cdt1 and MCM proteins. In S phase, Cdc45 and GINS are recruited to form the initiation complex. Elongation proceeds bidirectionally from replication forks, with leading strand synthesis continuous and lagging strand discontinuous via Okazaki fragments. Replication terminates at telomeres.
E. coli RNA polymerase is an enzyme that catalyzes the formation of phosphodiester bonds between nucleotides during transcription. It is composed of five subunits - two α subunits, one β subunit, one β' subunit, and one ω subunit. Together with a sigma factor, these subunits form the holoenzyme which is required for transcription initiation by binding to promoter sequences on DNA. The sigma factor recognizes specific promoter sequences and directs the holoenzyme to begin RNA synthesis. E. coli has multiple sigma factors that direct transcription of different genes depending on environmental conditions.
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 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.
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.
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.
DNA in cells can become damaged through radiation, chemicals, and errors during replication. There are several pathways cells use to repair DNA damage, including direct reversal, base excision repair, nucleotide excision repair, and mismatch repair. Double strand breaks can be repaired through direct joining of broken ends or homologous recombination using the sister chromatid as a template. Failure to properly repair DNA damage can lead to mutations and genetic disorders.
DNA repair system lecture that were prepered by Ph.D. students Mohammed Mohsen and Aliaa Hashim at microbiology department / college of medicine / babylon university.
1. DNA can be damaged through endogenous and exogenous sources. There are several mechanisms to repair DNA damage, including direct reversal, single strand break repair, and double strand break repair.
2. Single strand break repair mechanisms include base excision repair, nucleotide excision repair, and mismatch repair. Double strand break repair includes homologous recombination, non-homologous end joining, and microhomology-mediated end joining.
3. Defects in mismatch repair and homologous recombination through BRCA1/2 are important in gynecologic cancers.
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.
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.
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.
Nucleotide excision repair (NER) is a pathway that repairs a broad class of helix-distorting lesions in DNA that disrupt transcription and replication. It involves recognizing the damaged site, unwinding the DNA helix, making dual incisions on both sides of the damage, excising the damaged fragment, and resynthesizing the replacement DNA. NER is a complex process involving at least 28 genes and is important for repairing UV-induced damage and protecting against sunlight-induced DNA damage and cancer. Defects in NER genes can cause diseases like xeroderma pigmentosum, trichothiodystrophy, and Cockayne syndrome.
This document provides an overview of DNA repair mechanisms. It was authored by Arjun K B, a student at Kuvempu University's Sahyadri Science College Department of Biotechnology in Shimoga, India under the guidance of Dr. Prabhakar B T. The document contains an introduction to DNA structure and sources of DNA damage. It then discusses the importance of DNA repair in maintaining genomic integrity and preventing mutations that can lead to cancer. It proceeds to describe several DNA repair mechanisms in detail, including photoreactivation, base excision repair, mismatch repair, and SOS repair. The concluding section emphasizes the importance of an efficient DNA repair system for cell survival.
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.
DNA can be damaged through replication errors or environmental factors, potentially leading to cancer. However, cells have several DNA repair mechanisms to detect and fix damage before it causes mutations. These include proofreading during replication to fix mispaired bases, single-stranded break repair like base excision repair to remove and replace damaged nucleotides using the complementary strand as a template, and double-stranded break repair pathways like non-homologous end joining or homologous recombination to reconnect broken DNA strands. Together, these repair mechanisms help prevent mutations from occurring unless all repair fails, reducing cancer risk.
DNA is constantly damaged by radiation, reactive oxygen, and chemicals. To prevent mutations, cells have multiple DNA repair mechanisms. Base Excision Repair directly reverses some damage. Nucleotide Excision Repair and Mismatch Repair remove damaged areas and replace them. Failure to repair UV damage causes skin cancer in Xeroderma Pigmentosum patients. Defects in repair genes also cause Cockayne Syndrome and increased cancer risks. Overall, DNA repair maintains genetic integrity despite constant damage.
DNA is constantly damaged by radiation, reactive oxygen, and chemicals. To prevent mutations, cells have multiple DNA repair mechanisms. Base Excision Repair directly reverses some damage. Nucleotide Excision Repair and Mismatch Repair remove damaged areas and replace them. Failure to repair UV damage causes skin cancer in Xeroderma Pigmentosum patients. Defects in repair genes also cause Cockayne Syndrome and increased cancer risks. Overall, DNA repair maintains genetic integrity despite constant damage.
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.
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
Strategies for Effective Upskilling is a presentation by Chinwendu Peace in a Your Skill Boost Masterclass organisation by the Excellence Foundation for South Sudan on 08th and 09th June 2024 from 1 PM to 3 PM on each day.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
1. Dr Zahid Azeem
Assistant Professor
Biochemistry
AJK Medical College, Muzaffarabad
CMB-Module ---- Class- 2019
2. Introduction
Human body enjoys elaborate proofreading system
employed during DNA synthesis, errors—including
incorrect base-pairing or insertion of one to a few
extra nucleotides—can occur.
3. Damaging Agents (Mutagens)
The damaging agents can be either chemicals, for
example, nitrous acid, or radiation, for example,
ultraviolet light, which can fuse two pyrimidines
adjacent to each other in the DNA, and high energy
ionizing radiation, which can cause double-strand
breaks.
Bases are also altered or lost spontaneously from
mammalian DNA at a rate of many thousands per cell
per day.
4. • Radiations
o Highly reactive oxygen radicals produced
during normal cellular respiration as well as by
other biochemical pathways
o Ionizing radiation such as gamma rays and x-
rays
o Ultraviolet rays, especially the UV-C rays
(~260 nm) that are absorbed strongly by DNA but
also the longer-wavelength UV-B that penetrates
the ozone shield
Continue...
5. Agents that Damage DNAAgents that Damage DNA
• Chemicals in the environment
o Aromatic hydrocarbons, including some
found in cigarette smoke
o Plant and microbial products, e.g. the
Aflatoxin produced in moldy peanuts
o Chemicals used in chemotherapy,
especially chemotherapy of cancers.
7. 1 million individual lesions/cell/day
Heat
Metabolic accident
Radiation
Environment
depurination
But only 1/1000 accidental base
change results in a permanent
mutation
9. Danger of DNA damage
Structural damage -> prevent
replication/transcription
Stalling of replication fork
Harmful mutations -> impair survival of organism
Mutation in tumour suppressor genes for examples
• If unrepaired:
– Senescence
– Apoptosis
– Aberrant cell division -> cancer
10. DNA RepairDNA Repair
DNA repair can be grouped into two major functional
categories:
A) Direct Damage reversal
B) Excision of DNA damage
11. A) Direct Damage ReversalA) Direct Damage Reversal
The direct reversal of DNA damage is by far the
simplest repair mechanism that involves a single
polypeptide chain, with enzymatic properties
which binds to the damage and restores the DNA
genome to its normal state in a single-reaction
step. The major polypeptides involved in this
pathway are:
i) DNA photolyases, the enzymes responsible for
removing cyclobutane pyrimidine dimers from
DNA in a light-dependent process called as photo
reactivation
12.
13. Xeroderma pigmentosum (XP)Xeroderma pigmentosum (XP)
• Xeroderma pigmentosum (XP) is an
autosomal recessive genetic disease.
• The clinical syndrome includes marked
sensitivity to sunlight (ultraviolet) with
subsequent formation of multiple skin
cancers and premature death.
• The risk of developing skin cancer is
increased 1000- to 2000-fold.
• The inherited defect seems to involve the
repair of damaged DNA, particularly
thymine dimers.
• Cells cultured from patients with
xeroderma pigmentosum exhibit low
activity for the nucleotide excision-repair
process.
14. B) Excision of DNA damageB) Excision of DNA damage
i) Base excision repair (BER)
ii) Nucleotide excision repair (NER),
iii) Mismatch repair (MMR) and
iv) Strand break repairs.
• In these reactions a nucleotide segment containing
base damage, double-helix distortion or mispaired
bases is replaced by the normal nucleotide sequence
in a new DNA polymerase synthesis process.
• All of these pathways have been characterized in both
bacterial and eukaryotic organisms.
15. i) Base Excision Repair (BER)i) Base Excision Repair (BER)
BER is initiated by DNA glycosylases, which catalyze
the hydrolysis of the N-glycosidic bonds, linking
particular types of chemically altered bases to the
deoxyribose-phosphate backbone.
DNA damage is excised as free bases, generating sites
of base loss called apurinic or apyrimidinic (AP) sites.
16. i) Base Excision Repair (BER)i) Base Excision Repair (BER)
• The AP sites are substrates for AP endonucleases.
• These enzymes produce incisions in duplex DNA as a
result of the hydrolysis of a phosphodiester bond
immediately 5' or 3' to each AP site.
• The ribose-phosphate backbone is then removed from
the DNA through the action of a specific exonuclease
called deoxy ribophosphodiesterase or dRpase.
• Finally, the DNA polymerase and a ligase catalyze the
incorporation of a specific deoxyribonucleotide into
the repaired site, enabling correct base pairing
17. i) Base Excision Repair (BER)i) Base Excision Repair (BER)
Base excision-repair of DNA
• The enzyme uracil DNA glycosylase removes the
uracil created by spontaneous deamination of
cytosine in the DNA.
• An endonuclease cuts the backbone near the defect
• An endonuclease removes a few bases
• The defect is filled in by the action of a DNA
polymerase and
• The strand is rejoined by a ligase.
18.
19. ii) Nucleotide excision repairii) Nucleotide excision repair
(NER)(NER)
• This mechanism is used to replace regions of damaged
DNA up to 30 bases in length.
• Common causes of such DNA damage include ultraviolet
(UV) light, which induces the formation of cyclobutane
pyrimidine-pyrimidine dimers, and smoking, which causes
formation of benzo[a]pyrene-guanine adducts.
• Ionizing radiation, cancer chemotherapeutic agents, and a
variety of chemicals found in the environment cause base
modification, strand breaks, cross-linkage between bases
on opposite strands or between DNA and protein, and
numerous other defects.
• These are repaired by a process called nucleotide excision-
repair
20. ii) Nucleotide excision repairii) Nucleotide excision repair
(NER)(NER)
NER is a much more complex biochemical process
than BER, especially in eukaryotic cells.
Several gene products are required in a multiple step
process, during which the ordered assembly of DNA
proteins provides an enzymatic complex that
discriminates damaged from undamaged DNA.
21. ii) Nucleotide excision repairii) Nucleotide excision repair
(NER)(NER)
In eukaryotic cells the
enzymes cut between the
third to fifth phosphodiester
bond 3' from the lesion, and
on the 5' side the cut is
somewhere between the
twenty-first and twenty-fifth
bonds.
Thus, a fragment of DNA 27–
29 nucleotides long is excised.
After the strand is removed it
is replaced, again by exact
base pairing, through the
action of yet another
polymeras e,and the ends are
joined to the existing strands
by DNA ligase.
22. ii) Nucleotide excision repairii) Nucleotide excision repair
(NER)(NER)
• In Escherichia
coli there are three
specific proteins,
called UvrA, B and C,
involved in lesion
recognition and
endonuclease incision.
• This fragment is
released by UvrD
helicase action,
generating a gap that
is finally submitted to
repair synthesis
23. iii) Mismatch repair (MMR)iii) Mismatch repair (MMR)
• Mismatch repair corrects errors made when DNA is
copied.
• For example, a C could be inserted opposite an A, or
the polymerase could slip or stutter and insert two to
five extra unpaired bases.
• Specific proteins scan the newly synthesized DNA,
using adenine methylation within a GATC sequence
as the point of reference
• The template strand is methylated, and the newly
synthesized strand is not.
24. iii) Mismatch repair (MMR)iii) Mismatch repair (MMR)
• This difference allows the repair enzymes to identify
the strand that contains the errant nucleotide which
requires replacement.
• If a mismatch or small loop is found, a GATC
endonuclease cuts the strand bearing the mutation at
a site corresponding to the GATC.
• An exonuclease then digests this strand from the
GATC through the mutation, thus removing the
faulty DNA. This can occur from either end if the
defect is bracketed by two GATC sites.
• This defect is then filled in by normal cellular
enzymes according to base pairing rules
25.
26. iii) Mismatch repair (MMR) IN E.coliiii) Mismatch repair (MMR) IN E.coli
• In E coli, three proteins (Mutt S,
Mutt L, and Mutt H) are required
for recognition of the mutation
and nicking of the strand.
• Other cellular enzymes, including
ligase, polymerase, and SSBs,
remove and replace the strand.
• The process is more complicated
in mammalian cells, as about six
proteins are involved in the first
steps.
• Faulty mismatch repair has been
linked to hereditary nonpolyposis
colon cancer (HNPCC), one of the
most common inherited cancers.
28. B) Repairing Strand BreaksB) Repairing Strand Breaks
Ionizing radiation and certain chemicals can produce
both single-strand breaks (SSBs) and double-strand
breaks (DSBs) in the DNA backbone.
i) Single-Strand Breaks (SSBs)
Breaks in a single strand of the DNA molecule are
repaired using the same enzyme systems that are used
in Base-Excision Repair (BER).
29. B) Repairing Strand BreaksB) Repairing Strand Breaks
ii) Double-Strand Break Repair
• There are two mechanisms by which the cell attempts
to repair a complete break in a DNA molecule:
• 1) Direct joining of the broken ends. This requires
proteins that recognize and bind to the exposed ends
and bring them together for ligating. This type of
joining is also called Nonhomologous End-
Joining (NHEJ). A protein called Ku is essential for
NHEJ.
30. B) Repairing Strand BreaksB) Repairing Strand Breaks
Errors in direct joining may be a cause of the
various translocations that are associated with
cancers. Examples:
Burkitt's lymphoma
Philadelphia chromosome in chronic myelogenous
leukemia (CML)
B-cell leukemia
31. B) Repairing Strand BreaksB) Repairing Strand Breaks
Meiosis also involves
DSBs
Recombination
between homologous
chromosomes in
meiosis I also involves
the formation of DSBs
and their repair.
Meiosis I with the
alignment of
homologous
sequences provides a
mechanism for
repairing damaged
DNA.
32. Diseases associated with defectiveDiseases associated with defective
DNA repair systemDNA repair system
33. ProgeriaProgeria
Progeria (Hutchinson-Gilford Progeria
Syndrome) is an extremely rare genetic disorder
that causes the affected individual to undergo
advanced aging at an early age.
The symptoms closely resemble aging and
include wrinkles, hair loss, and delayed growth.
Affected individuals have normal development
up to 18 months and suddenly stop gaining
weight and display stunted height.
As the individual ages, Progeria becomes more
severe with an average life expectancy of 12
years.
34. Werner syndrome(Adult Progeria)Werner syndrome(Adult Progeria)
syndromesyndrome
Werner syndrome is a hereditary condition associated
with premature aging and an increased risk of cancer and
other diseases. The signs of Werner syndrome usually
develop in the teenage years.
A person with Werner syndrome does not have the usual
growth spurt typical of a teenager and is shorter on
average. Signs of aging, including gray hair and hair loss,
may appear in the 20's.