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 replication is an important process which takes place in every organisms, be it prokaryotic or eukaryotic. The DNA replication process produces two identical copies of daughter DNA molecules using the existing DNA molecule as template. Each daughter DNA molecule inherits one strand from the parent cell and the other strand is newly synthesized. This is known as semiconservative mode of replication, demonstrated by Meselson and Stahl.
This presentation is about Genomic imprinting. Genomic imprinting is only found in eutherians. In next few slides we'll try to understand this phenomena.
It is the process of synthesis of protein by encoding information on mRNA.
Protein synthesis requires mRNA, tRNA, aminoacids, ribosome and enzyme aminoacyl tRNA synthase
DNA replication is an important process which takes place in every organisms, be it prokaryotic or eukaryotic. The DNA replication process produces two identical copies of daughter DNA molecules using the existing DNA molecule as template. Each daughter DNA molecule inherits one strand from the parent cell and the other strand is newly synthesized. This is known as semiconservative mode of replication, demonstrated by Meselson and Stahl.
This presentation is about Genomic imprinting. Genomic imprinting is only found in eutherians. In next few slides we'll try to understand this phenomena.
It is the process of synthesis of protein by encoding information on mRNA.
Protein synthesis requires mRNA, tRNA, aminoacids, ribosome and enzyme aminoacyl tRNA synthase
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.
Describe the repair mechanisms used during DNA replication.Soluti.pdfkellenaowardstrigl34
Describe the repair mechanisms used during DNA replication.
Solution
DNA like any other molecule can undergo a variety of chemical reactions. Because DNA
uniquely serves as a permanent copy of the cell genome, however, changes in its structure are of
much greater consequence than are alterations in other cell components, i.e RNA’s and Proteins.
Mutations can consider the incorporation of incorrect bases during DNA replication. And also,
various chemical changes occur in DNA either spontaneously or as a result of exposure to
chemicals or radiation. Such damage to DNA can block replication or transcription, and can
result in a high frequency of mutations—consequences that are unacceptable from the standpoint
of cell reproduction.
To maintain the integrity of their genomes, cells have therefore had to evolve mechanisms to
repair damaged DNA. DNA repair mechanism can be divided into two general classes: (1) direct
reversal of the chemical reaction responsible for DNA damage, and (2) removal of the damaged
bases followed by their replacement with newly synthesized DNA. The rate of DNA repair is
dependent on many factors, including the cell type, the age of the cell, and the extracellular
environment. A cell that has accumulated a large amount of DNA damage, or one that no longer
effectively repairs damage incurred to its DNA, can enter one of three possible states:
1. an irreversible state of dormancy, known as senescence
2. cell suicide, also known as apoptosis or programmed cell death
3. unregulated cell division, which can lead to the formation of a tumor that is cancerous
The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal
functionality of that organism.
Direct reversal
Cells are known to eliminate three types of damage to their DNA by chemically reversing it.
These mechanisms do not require a template,the types of damage they counteract can occur in
only one of the four bases. Such direct reversal mechanisms are specific to the type of damage
incurred and do not involve breakage of the phosphodiester backbone. The formation of
pyrimidine dimers upon irradiation with UV light results in an abnormal covalent bond between
adjacent pyrimidine bases. The photo reactivation process directly reverses this damage by the
action of the enzyme photolyase, whose activation is obligately dependent on energy absorbed
from blue/UV light (300–500 nm wavelength) to promote catalysis.
The second type of damage, methylation of guanine bases, is directly reversed by the protein
methyl guanine methyl transferase (MGMT),
The third type of DNA damage reversed by cells is certain methylation of the bases cytosine and
adenine.
Excision Repair mechanisms
Single strand damage:
When only one of the two strands of a double helix has a defect, the other strand can be used as a
template to guide the correction of the damaged strand. In order to repair damage to one of the
two paired molecules of DNA, there exist a number of excis.
Each day the genome is subjected to thousands of DNA damaging events from diverse sources which can have potentially deleterious consequences. In order to maintain genome integrity eukaryotic cells have evolved a highly complex and multifaceted response network called the DNA damage response, or ?DDR?....
Each day the genome is subjected to thousands of DNA damaging events from diverse sources which can have potentially deleterious consequences. In order to maintain genome integrity eukaryotic cells have evolved a highly complex and multifaceted response network called the DNA damage response, or ?DDR?
Each day the genome is subjected to thousands of DNA damaging events from diverse sources which can have potentially deleterious consequences. In order to maintain genome integrity eukaryotic cells have evolved a highly complex and multifaceted response network called the DNA damage response, or ?DDR?....
Each day the genome is subjected to thousands of DNA damaging events from div...semualkaira
Each day the genome is subjected to thousands of DNA damaging events from diverse sources which can have potentially deleterious consequences. In order to maintain genome integrity eukaryotic cells have evolved a highly complex and multifaceted response network called the DNA damage response, or ?DDR?..
Each day the genome is subjected to thousands of DNA damaging events from diverse sources which can have potentially deleterious consequences. In order to maintain genome integrity eukaryotic cells have evolved a highly complex and multifaceted response network called the DNA damage response
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
2. • DNA repair is a collection of processes by which a cell identifies and corrects damage
to the DNA molecules that encode its genome. In human cells, both normal metabolic
activities and environmental factors such as radiation can cause DNA damage, resulting
in as many as 1 million individual molecular lesions per cell per day.
• Many of these lesions cause structural damage to the DNA molecule and can alter or
eliminate the cell's ability to transcribe the gene that the affected DNA encodes.
• When normal repair processes fail, and when cellular apoptosis does not occur,
irreparable DNA damage may occur, including double-strand breaks and DNA cross
linkages (interstrand crosslinks or ICLs)
3. 1. Direct reversal of the chemical reaction responsible for DNA damage, and
2. Removal of the damaged bases followed by their replacement with newly
synthesized DNA. Where DNA repair fails
The mechanisms of DNA repair can be divided into two general classes:
4. Mechanisms of DNA Repair
1. Direct Reversal of DNA Damage
• Only a few types of DNA damage are repaired in this way, particularly pyrimidine
dimers resulting from exposure to ultraviolet (UV) light and alkylated guanine
residues that have been modified by the addition of methyl (CH3) or ethyl (CH2-
CH3) groups at the O6 position of the purine ring.
• The major type of damage induced by UV light is the formation of pyrimidine
dimers, in which adjacent pyrimidines on the same strand of DNA are joined by
the formation of a cyclobutane ring resulting from saturation of the double bonds
between carbons 5 and 6.
5. • The formation of such dimers distorts:-
1. the structure of the DNA chain.
2. blocks transcription or replication past the site of damage, so their repair is
closely correlated with the ability of cells to survive UV irradiation.
• One mechanism of repairing UV-induced pyrimidine dimers is direct reversal of
the dimerization reaction. The process is called photoreactivation because energy
derived from visible light is utilized to break the cyclobutane ring structure.
6. Direct repair of thymine dimers. UV-induced thymine dimers can be repaired by photoreactivation, in which
energy from visible light is used to split the bonds forming the cyclobutane ring (double bond).
7. • The second form of direct repair deals with damage resulting from the reaction between
alkylating agents and DNA.
• Alkylating agents are reactive compounds that can transfer methyl or ethyl groups to a
DNA base, thereby chemically modifying the base.
• The principle of damage process?
• Methylation of o6 position of Guanine O6 methyl Guanine form complementary
base pairing with T instead of C
• Rapier mechanism by:-
• Enzyme called O6 methylguanine methyltransferase transfer methyl group from o6
methylguanine to Cysteine residues in its active site.
• As a result the original guanine is restored.
9. Single strand damage
• In excision repair, the damaged DNA is recognized and removed, either as free bases or
as nucleotides.
• The resulting gap is then filled in by synthesis of a new DNA strand, using the
undamaged complementary strand as a template.
• Three types of excision repair:-
1. Base -excision repair.
2. nucleotide-excision repair.
3. mismatch repair.
• Enable cells to cope with a variety of different kinds of DNA damage.
10. • The uracil-containing DNA can be repaired by base-excision repair, in which single
damaged bases are recognized and removed from the DNA molecule . Uracil can arise
in DNA by two mechanisms:-
• (1) Uracil (as dUTP [deoxyuridine triphosphate]) is occasionally incorporated in place
of thymine during DNA synthesis.
• (2) uracil can be formed in DNA by the deamination of cytosine (result in formation of
Uracil )
• The second mechanism is of much greater biological significance because it alters the
normal pattern of complementary base pairing and thus represents a mutagenic event
A- Base-excision repair
11. DNA glycosylase
DNA polymerase
Deoxyribose phosphodiesterase
AP endonuclease
Ligase
1. DNA glycosylase cleave the bond ( glycosidic bond) that
link U to deoxyribose of DNA backbone
2. This yield apyrimidinic site (AP site) its mean sugar without base attach + free Uracil
3. AP endonuclease recognized AP site and repairing it by cleaved adjacent to AP site
4. Deoxyribose phosphodiesterase remove remaining deoxyribose
5. Gap filled by DNA polymerase and sealed by the action of ligase
6. The result is incorporating of correct base C opposite to G
DNA containing U formed by deamination of C
AP Site
12.
13. B- nucleotide-excision repair
Recognize a wide variety of damaged bases that distort the DNA molecule,
including UV-induced pyrimidine dimers and bulky groups added to DNA bases
as a result of the reaction of many carcinogens with DNA
• Why it is named by this name ?
• because the damaged bases (e.g., a thymine dimer) are removed as part of an
oligonucleotide containing the lesion.
14. DNA Polymerase
oligonucleotide
Damage recognition
nucleotide cleavage
Helicase Excised
Ligase
1. UV - induced pyramiding dimer
2. Damaged DNA is recognized and then cleaved on
both sides of a thymine dimer by 3′ and 5′ nucleases
3. Unwinding by a helicase results in excision of oligonucleotide
containing the damaged bases
4. The result gap is filled by DNA polymerase and sealed by ligase
15. 1. uvr A recognize damage site recruit uvr B+uvr C.
2. uvr B+uvr C cleave on 3 and 5 side of damaged site and the (Uvr B+C)
Excising oligonucleotide consisting 12 or 13 bases.
3. Helicase (uvr D) required to remove damaged
containing oligonucleotide from ds DNA molecules
4. Gap filled by DNA polymerase I and sealed by Ligase
In E. coli, nucleotide-excision repair is catalyzed by the products of three
genes (uvrA, B, and C)
uvrA
uvrB uvrC
16. • Nucleotide-excision repair systems have also been studied extensively in
eukaryotes, particularly in yeasts and in humans. In yeasts, as in E. coli, several
genes involved in DNA repair (called RAD genes for radiation sensitivity) have
been identified by the isolation of mutants with increased sensitivity to UV light.
• In humans, DNA repair genes have been identified largely by studies of
individuals suffering from inherited diseases resulting from deficiencies in the
ability to repair DNA damage. The most extensively studied of these diseases is
xeroderma pigmentosum (XP), a rare genetic disorder that affects approximately
one in 250,000 people. Individuals with this disease are extremely sensitive to
UV light and develop multiple skin cancers on the regions of their bodies that are
exposed to sunlight.
20. In E. coli, the ability of the mismatch repair system to distinguish
between parental DNA and newly synthesized DNA is based on the fact
that DNA of this bacterium is modified by the methylation of adenine
residues within the sequence GATC to form 6- methyladenine
Since methylation occurs after replication, newly synthesized DNA
strands are not methylated and thus can be specifically recognized by
the mismatch repair enzymes
Mismatch repair is initiated by the protein MutS, which recognizes
the mismatch and forms a complex with two other proteins called
MutL and MutH
The MutH endonuclease then cleaves the unmethylated DNA strand at
a GATC sequence
MutL and MutS then act together with an exonuclease and a helicase
(uvr D) to excise the DNA between the strand break and the mismatch
Resulting gap being filled by DNA polymerase and sealed by ligase.
23. In mammalian cells, it appears that the strand-specificity of mismatch
repair is determined by the presence of single-strand breaks (which
would be present in newly replicated DNA) in the strand to be repaired
The eukaryotic homologs of MutS and MutL then bind to the
mismatched base and direct excision of the DNA between the strand
break and the mismatch, as in E. coli
The importance of this repair system is dramatically illustrated by the
fact that mutations in the human homologs of MutS and MutL are
responsible for a common type of inherited colon cancer (hereditary
nonpolyposis colorectal cancer, or HNPCC)
HNPCC is one of the most common inherited diseases; it affects as
many as one in 200 people and is responsible for about 15% of all
colorectal cancers in this country
24.
25. The repair of damage to both DNA strands is particularly important in maintaining genomic integrity.
There are two main mechanisms for repairing double strand breaks: homologous recombination (HR) and classical
nonhomologous end joining(NHEJ).
HR relies on undamaged template DNA as reference to repair the DSB, resulting in the restoration of the original sequence.
NHEJ modifies and ligates the damaged ends regardless of homology
DSB can occur naturally due to the presence of reactive species generated by metabolism, and various external factors (e.g.
ionizing radiation or chemotherapeutic drugs).
In mammalian cells, there are numerous cellular processes that induce DSB :-
Firstly, DNA topological strain from topoisomerase during normal cell growth can cause the majority a cell’s DSB.
Secondly, cellular processes such as meiosis and the maturation of antibodies can cause nuclease-induced DSB.
Thirdly, the cleavage of different DNA structures such as reversed or blocked DNA replication forks, and DNA interstrand
crosslinks (ICLs) can also cause DSB
DNA double strand break repair
27. The chromosome formation occurs when the cell in
dividing state in S/G2 phase
These 3 proteins (RAD 50+MRE11) come in contact with 5’
end .The function of MRN complex in DNA end resection ,pick
5’ end and make resection of thousand nucleotide leaving 3’
overhang
The next protein RAD51 take help of BRCA 2 and
replace RPA on strand, function is help in search for
homologous DNA and help in process of invasion
Small different proteins that can cover single strand DNA are
called as Replication protein A(RPA), The function of RPA is
to protect ssDNA from nucleases and to prevent them from
coiling back again.
28. The invasion process lead to formation of D- loop
The 3’ end use the strand as a template, once the
replication process complete, the termination
process start
There are two option
first called Non- cross over HR repair :- all
homologous chromosomes will be like they were
before.
Or, they exchanged part with each other and called
cross- over HR repair
29.
30. KU- 70/80 detect or recognize the broken DNA ends, protect them from
nuclease activity and bind to DSB and recruit DNA-Pkcs
DNA-Pkcs undergo auto-phosphorylation favoring the process of DNA
ends by Artemis which trims single strand overhangs due to it has
(exonuclease activity).
Where DNA-PKcs refer to (Protein Kinase Catalytic Subunit).
DNA ligase IV + XRCC4 + XLF complex ligate the
processed DNA ends
XLF : stimulate Ligase IV activity, aiding in DSB by
formation of filament between XRCC4 and XLF.
XRCC4: DNA repair protein and stabilize Ligase IV.
This entire complex lead to fixation of dsDNA breaks.
DNA Ligase IV help in repair ds breaks during lymphocyte
receptor development.
Other factors (AFLP+PNKP) help in fixation
Non-homologous end joining
31.
32.
33.
34.
35. SOS Repair
SOS repair or “bypass” or “Emergency” repair is one of the DNA repair mechanisms.
SOS repair primarily recovers the DNA damage caused due to environmental stresses.
It serves as a regulatory system, which comprises many complex inducer proteins that
repair the damaged DNA
SOS system also includes a repressor protein, namely LexA. The RecA protein floats
around the cell, which regulates the activity of LexA protein.
The RecA regulatory protein mediates the repression or expression of LexA repressor
“SOS response system” refers to the mechanism in which an organism initiates the
production of activator protein (RecA), which results in the dissociation of LexA
repressor and activates the SOS inducer proteins.
36. It stands for “Save Our Soul”. The SOS system remains repressed until the conversion of RecA protein into RecA
protease.
It does not repair the DNA damage completely but provides tolerance ability to the affected organism.
In normal DNA, LexA acts as a repressor protein that
binds to the particular site of DNA or SOS box. The
binding will repress the activity of SOS genes.
But in mutated DNA, RecA acts as an activator of SOS
genes in the SOS system, which causes proteolysis of
the repressor protein and allows the SOS genes
expression into different DNA repairing inducer
proteins.
37. Mechanism of SOS Repair 1. In case of excessive DNA damage, stress conditions etc., a cell
responds by activating signal or RecA protein. It floats in the vicinity
of the cell in search of any damage in the DNA.
2. A RecA protein specifically binds to the single stranded DNA. On
binding with the single stranded DNA fragments, RecA forms a
filament like structure around the DNA.
3. Then, a LexA repressor comes in contact with the nucleoprotein
filament assembled by the RecA protein. When RecA interacts with
the repressor protein, it converts into RecA protease.
4. The formation of RecA protease causes autocatalytic proteolysis of
LexA repressor protein. Thus, a LexA protein could not bind with the
SOS operator.
5. Inactivation of LexA protein activates the inducer proteins that
repair the DNA damage but alters the DNA sequence.
6. After DNA repair, the RecA protein loses its efficiency to cause
proteolysis, and the LexA protein will again bind to the SOS operator
or switch off the SOS system.
38. SOS system only activates in case of excessive DNA damage, leading to single strand breakage at the replication fork. This DNA
damage activates the RecA regulatory protein that links with the single stranded DNA through the cellular energy ATP.
RecA protein and ssDNA attachment will give rise to a right-handed nucleoprotein complex or = “RecA + ssDNA filament”.
The interaction of LexA repressor with the nucleoprotein complex causes proteolytic cleavage of LexA dimer.
Proteolytic cleavage is due to the conversion of RecA protein into protease, which suppresses LexA protein’s activity.
The SOS box genes will now express into different inducer proteins to recover the damaged DNA.
The expression of inducer proteins will not occur all at once but express relatively to the type of DNA damage. Therefore, an
SOS system switches on and off in the presence and absence of activator RecA protein, respectively.
SOS conclusion
Rec A ssDNA
Nucleoprotein
filament
LexA
repressor
proteolytic
cleavage
of LexA
RecA
protease
39. SOS Inactivation
An SOS system always switches off when a DNA is healthy. The
LexA promoter produces LexA repressor protein. The association
of LexA repressor to the consensus sequence (having 20 base
pairs of the SOS-box) suppresses the functioning of the SOS
system. Thus, LexA blocks the SOS box, which arrests the activity
of SOS genes that participate in the recovery of damaged DNA.
SOS activation
The SOS repair system comes into action when the DNA is not
normal, and all the repair system fails. The organisms activate
the SOS system by themselves in response to the damage against
UV-light or any other factors