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Questions and Answers
What mechanism involves alignment and crossover of damaged chromosome fragments with their homologues?
What mechanism involves alignment and crossover of damaged chromosome fragments with their homologues?
Which repair method is characterized by the potential loss of nucleotides at the site of DNA damage?
Which repair method is characterized by the potential loss of nucleotides at the site of DNA damage?
Which of the following repair systems directly reverses damage without requiring a template?
Which of the following repair systems directly reverses damage without requiring a template?
Which lesion is specifically recognized and subjected to Base Excision Repair?
Which lesion is specifically recognized and subjected to Base Excision Repair?
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In the context of DNA repair, what do Ku proteins primarily facilitate?
In the context of DNA repair, what do Ku proteins primarily facilitate?
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What is the primary source of spontaneous DNA damage during replication?
What is the primary source of spontaneous DNA damage during replication?
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Which type of DNA damage is specifically characterized by the alteration of base pairing due to a shift in form?
Which type of DNA damage is specifically characterized by the alteration of base pairing due to a shift in form?
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How does the error rate of DNA replication decrease due to repair systems?
How does the error rate of DNA replication decrease due to repair systems?
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Which of the following is NOT a source of induced DNA damage?
Which of the following is NOT a source of induced DNA damage?
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What is a common outcome of insertion mutations caused by strand slippage during replication?
What is a common outcome of insertion mutations caused by strand slippage during replication?
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Which of the following statements about tautomerisation is true?
Which of the following statements about tautomerisation is true?
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In which type of DNA damage does deamination play a role?
In which type of DNA damage does deamination play a role?
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Trinucleotide repeat expansions are often linked to which type of DNA damage?
Trinucleotide repeat expansions are often linked to which type of DNA damage?
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What is the main consequence of deamination of cytosine?
What is the main consequence of deamination of cytosine?
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Which of the following bases is formed from the deamination of adenine?
Which of the following bases is formed from the deamination of adenine?
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What type of mutagen is ethidium bromide classified as?
What type of mutagen is ethidium bromide classified as?
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Which mutation occurs when an intercalating agent inserts between bases?
Which mutation occurs when an intercalating agent inserts between bases?
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What is the likelihood of purine glycosidic bonds hydrolyzing compared to pyrimidine glycosidic bonds?
What is the likelihood of purine glycosidic bonds hydrolyzing compared to pyrimidine glycosidic bonds?
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What effect does 5-methylcytosine conversion to thymine have on DNA?
What effect does 5-methylcytosine conversion to thymine have on DNA?
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Which of these is an example of a base analogue?
Which of these is an example of a base analogue?
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What is the primary consequence of depurination in DNA?
What is the primary consequence of depurination in DNA?
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Which of the following agents is known as a deaminating agent?
Which of the following agents is known as a deaminating agent?
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What type of damage is primarily caused by alkylation?
What type of damage is primarily caused by alkylation?
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What is the primary effect of UV light on DNA?
What is the primary effect of UV light on DNA?
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Which chemical agent is classified as an oxidizing agent?
Which chemical agent is classified as an oxidizing agent?
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What is the estimated number of depurination events per human cell per day?
What is the estimated number of depurination events per human cell per day?
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How do γ and X rays affect DNA?
How do γ and X rays affect DNA?
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Which type of mutation is most commonly associated with oxidative damage?
Which type of mutation is most commonly associated with oxidative damage?
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What is the total estimated rate of DNA damaging events per cell per day?
What is the total estimated rate of DNA damaging events per cell per day?
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Which type of DNA damage is typically associated with ionizing radiation?
Which type of DNA damage is typically associated with ionizing radiation?
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Which of these alterations reflects an oxidative base damage product?
Which of these alterations reflects an oxidative base damage product?
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Study Notes
DNA Repair Lectures 8-9
- DNA repair lectures cover sources and types of DNA damage, and repair mechanisms.
DNA Damage - Types
- Abnormal base pairs
- Base pair mismatches
- Single-strand breaks
- Double-strand breaks
- Thymine dimers
- Nucleotide insertions
- Nucleotide deletions
- Abasic sites
- DNA cross-links
- Chemical adducts
DNA Damage - Sources
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Spontaneous Sources:
- Replication errors: Errors in DNA replication introduce incorrect bases, once every 107 base pairs (even with proof-reading); repair systems reduce this error rate to 10-10. Some repetitive regions can lead to slippage (insertion of repeats that cannot be repaired).
- Tautomerisation: Shifting of bases between keto and enol forms causes mispairing (e.g., T incorrectly pairs with G). This mutation is consolidated during the next replication cycle.
- Deamination: Loss of an amino group from a base, changing its identity (e.g., C to U, A to hypoxanthine, G to xanthine); ~100 C-to-U mutations per cell per day, A & G deaminations are rarer (~1/day). 5-Methyl-C -> T cannot be repaired.
- Depurination: Loss of a purine base (A or G) from the DNA; forms an abasic site (apurinic) and is ~10,000 purine glycosidic bonds hydrolyzed/cell/day, ~600 pyrimidine glycosidic bonds/cell/day which is 4 times more likely in single stranded DNA.
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Induced Sources:
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Mutagens: Substances that increase the rate of mutations.
- Ames test: Used to identify mutagens, a chemical is tested to see if it causes mutations in bacteria and if a high number of revertants result, the chemical is a mutagen.
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Chemical Mutagens:
- Intercalating agents, e.g., ethidium bromide – Insert themselves between bases causing insertion/deletion mutations in DNA.
- Base analogues, e.g., bromouracil – Incorporated into DNA, prone to tautomeric shifts causing mispairing and mutations.
- Alkylating agents, e.g., nitrosamines, methyl bromide – Add alkyl groups to nucleobases, such as G to O6-methyl-G, changing base pairing.
- Deaminating agents, e.g., nitrous acid - Remove amino groups.
- Oxidizing agents, e.g., superoxide ion, H2O2 - Causes many possible nucleotide alterations. Also generates 8-oxo-G, which pairs with A instead of C.
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Physical Mutagens:
- UV light: Induces thymine dimers, preventing proper base pairing in DNA.
- Radiation (e.g., γ and X-rays): Breaks bonds, creates free radicals, causing single/double strand breaks; significant bases chemically altered/linked or detached.
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Mutagens: Substances that increase the rate of mutations.
DNA Damage - Rates
- High estimates of various kinds of DNA damage per cell per day.
Repair Systems
- General Mechanisms: Repair systems can correct replication errors, deaminations, oxidative damage, alkylation, thymine dimers etc.
- Pathways for DNA repair in response to various damaging agents. Direct reversal, Base excision repair (BER), Nucleotide excision repair (NER), Mismatch repair (MMR), Non-homologous end joining (NHEJ), Homologous recombination (HR)
- Homologous recombination: For double-stranded breaks; fragments of the damaged chromosome are aligned to a homologous (i.e., similar) chromosome, and then crossed over with it.
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Non-homologous end joining: Damaged ends are joined by specialized enzymes.
- Risk of deleterious consequences (loss of segments of the DNA, insertions of sequences) from a non-homologous repair.
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Description
Explore the critical aspects of DNA repair mechanisms, including various types and sources of DNA damage. This quiz delves into specific damage types such as base pair mismatches and double-strand breaks, alongside spontaneous and induced damage sources. Test your understanding of how cells maintain genetic integrity through repair systems.