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Mismatch Repair in Eukaryotes and Cancer
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Mismatch Repair in Eukaryotes and Cancer

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@DeadCheapBaritoneSaxophone

Questions and Answers

What is the role of methyltransferase in DNA damage repair?

  • It directly pairs thymine with cytosine during replication.
  • It repairs single base changes by adding nucleotides.
  • It transfers a methyl group to a guanine base. (correct)
  • It catalyzes the removal of damaged bases.

    • Which base pair swap occurs if O6-methylguanine is not repaired?

  • Cytosine pairs with uracil.
  • Guanine pairs with thymine. (correct)
  • Adenine pairs with thymine.
  • Guanine pairs with cytosine.

    • What type of DNA repair involves removing a patch of nucleotides?

  • Base excision repair
  • Nucleotide excision repair (correct)
  • Methylation repair
  • Mismatch repair

    • What triggers the action of DNA glycosylases in base excision repair?

    <p>Identification of a specific damaged base.</p> Signup and view all the answers

    What common chemical reaction is often repaired by the base excision mechanism?

    <p>Depurination and deamination</p> Signup and view all the answers

    What is the result of deamination of cytosine in DNA?

    <p>It converts cytosine into uracil.</p> Signup and view all the answers

    Which enzyme recognizes the missing base after DNA glycosylase acts?

    <p>AP endonuclease</p> Signup and view all the answers

    What is produced when purine bases are lost from DNA during depurination?

    <p>An abasic site</p> Signup and view all the answers

    What role do DNA polymerase and DNA ligase play in nucleotide excision repair?

    <p>They repair the gap produced in the DNA helix.</p> Signup and view all the answers

    What type of DNA damage does nucleotide excision repair specifically target?

    <p>Bulky lesions from covalent reactions with carcinogens.</p> Signup and view all the answers

    How does the nucleotide excision repair mechanism identify DNA damage?

    <p>Through a large multienzyme complex scanning for distortions.</p> Signup and view all the answers

    What condition is associated with a malfunction in the nucleotide excision repair pathway?

    <p>Xeroderma pigmentosum.</p> Signup and view all the answers

    What can happen if double-strand breaks in DNA are not repaired?

    <p>Chromosome fragmentation and gene loss.</p> Signup and view all the answers

    Which of the following can cause double-strand breaks in DNA?

    <p>Ionizing radiation and oxidative free radicals.</p> Signup and view all the answers

    What type of damage can be caused by intercalating agents like ethidium bromide?

    <p>Structural distortion of DNA</p> Signup and view all the answers

    What does the term 'damage bypass' refer to in cellular responses to DNA damage?

    <p>Translesion synthesis using error-prone polymerases</p> Signup and view all the answers

    What is the consequence of thymine dimers in the context of DNA repair deficiencies?

    <p>They lead to mutations and skin cancer if not repaired.</p> Signup and view all the answers

    Which mechanism directly reverses thymine-thymine dimers in DNA?

    <p>Photoreactivation by DNA photolyase</p> Signup and view all the answers

    How does a DNA helicase contribute to the nucleotide excision repair process?

    <p>It unwinds the DNA strand to remove damaged sections.</p> Signup and view all the answers

    What is the most severe type of DNA damage that can occur?

    <p>Double-stranded DNA breaks</p> Signup and view all the answers

    What is the primary role of mismatch repair in eukaryotic cells?

    <p>To identify and repair mismatched bases</p> Signup and view all the answers

    Which mutation is commonly associated with hereditary nonpolyposis colorectal cancer?

    <p>Mutations in mismatch repair proteins</p> Signup and view all the answers

    Which DNA polymerase is responsible for translesion synthesis past TT dimers?

    <p>DNA polymerase eta</p> Signup and view all the answers

    What kind of DNA damage is generated by the loss of a nitrogenous base from a nucleotide?

    <p>Abasic sites</p> Signup and view all the answers

    What is a potential outcome of accumulated mutations due to defective mismatch repair?

    <p>Development of tumors in specific tissues</p> Signup and view all the answers

    Which type of repair mechanism can directly reverse DNA damage without nucleolytic excision?

    <p>Direct reversal of damage</p> Signup and view all the answers

    Which chemical agent is known for causing an increase in the rate of mutation?

    <p>Nitrosamines</p> Signup and view all the answers

    Which type of DNA damage typically requires repair due to spontaneous alterations?

    <p>Oxidative damage</p> Signup and view all the answers

    What type of damage does a T-T dimer represent?

    <p>Structural distortion</p> Signup and view all the answers

    What is the significance of methylated cytosines in DNA?

    <p>They are hotspots for spontaneous mutation.</p> Signup and view all the answers

    Which of the following best describes deamination?

    <p>A hydrolytic damage that affects single base pairs</p> Signup and view all the answers

    What type of DNA damage typically results from UV radiation?

    <p>Dimer formation between adjacent bases</p> Signup and view all the answers

    What is the primary mechanism through which homologous recombination repairs DNA?

    <p>It retrieves genetic information from an undamaged homologous chromosome.</p> Signup and view all the answers

    During which phases of the cell cycle does homologous recombination primarily occur?

    <p>S and G2 phases</p> Signup and view all the answers

    What characterizes nonhomologous end joining compared to homologous recombination?

    <p>It can lead to the loss of nucleotides at the site of joining.</p> Signup and view all the answers

    Which condition is associated with failures in DNA recombination repair enzymes?

    <p>Fanconi’s anemia</p> Signup and view all the answers

    What is one main effect of DNA damage on the cell cycle?

    <p>It delays progression of the cell cycle until repairs are complete.</p> Signup and view all the answers

    What happens during nonhomologous end joining when DNA is damaged?

    <p>It joins the broken ends without a template, potentially causing mutations.</p> Signup and view all the answers

    Which phases of the cell cycle can DNA damage impact?

    <p>G1 into S phase, S phase, and G2 into M phase</p> Signup and view all the answers

    Why is nonhomologous end joining particularly important before DNA has been replicated?

    <p>There is no available template for homologous repair.</p> Signup and view all the answers

    Study Notes

    Mismatch Repair in Eukaryotes

    • Original DNA strand identification relies on recognizing nicks in newly synthesized DNA.
    • Lynch Syndrome, a hereditary nonpolyposis colorectal cancer, results from mutations in mismatch repair proteins, leading to rapid accumulation of mutations and tumor development.

    General Classes of DNA Damage

    • Spontaneous DNA damage can occur due to the action of water in cells.
    • A mutagen increases mutation rates beyond spontaneous levels.
    • Three main DNA damage classes:
      • Single base changes
      • Structural distortion
      • DNA backbone damage

    Single Base Changes

    • Single base changes affect DNA sequence slightly.
    • Deamination, converting 5-methylcytosine to thymine, is a common mutation source.
    • Alkylating agents like nitrosamines can create O6-methylguanosine, which mispairs with thymine, potentially causing mutations.

    Structural Distortion

    • UV radiation causes cyclobutane ring formation between adjacent thymines, leading to T-T dimers that distort the DNA structure.
    • Intercalating agents, such as ethidium bromide, insert between DNA bases, causing structural issues.
    • Bulky adducts from chemical mutagens can also lead to distortions in DNA structure.

    DNA Backbone Damage

    • Abasic sites result from the loss of a nitrogenous base, often generated by unstable base adducts.
    • Double-stranded DNA breaks, the most severe damage type, can be caused by ionizing radiation and various chemicals.

    Cellular Responses to DNA Damage

    • Cells can perform damage bypass, damage reversal, or damage removal.
    • Translesion synthesis (TLS) allows specialized DNA polymerases to replicate past DNA damage, but with higher error rates.

    DNA Repair Mechanisms

    • DNA stability is crucial for genetic information, necessitating complex repair processes for spontaneous changes.
    • Repair processes include direct damage reversal, excision repair, and double-stranded break repair.

    Direct Reversal of DNA Damage

    • UV-induced thymine dimers can be repaired directly by DNA photolyase, utilizing light energy.
    • Methyltransferase removes methyl groups from O6-methylguanine to restore proper base pairing with cytosine.

    Excision Repair Mechanisms

    • Base excision repair removes damaged bases via DNA glycosylases, addressing issues like depurination and deamination.
    • Nucleotide excision repair addresses larger DNA distortions from various sources, including UV damage and bulky lesions.

    Xeroderma Pigmentosum

    • Caused by mutations in nucleotide excision repair pathways, leading to extreme UV sensitivity and high skin cancer risk.

    Double-Strand Break Repair

    • Two main pathways for repairing double-strand breaks: homologous recombination and nonhomologous end joining.
    • Homologous recombination uses an undamaged homologous chromosome to accurately repair damage.
    • Nonhomologous end joining joins broken ends of DNA with potential nucleotide loss and increased mutation risk.

    Cell Cycle Delay Due to DNA Damage

    • Eukaryotic cells delay the cell cycle to ensure complete DNA repair, blocking transitions between critical phases (G1 to S, S phase progression, G2 to M) in the presence of damage.

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    Description

    Explore the critical processes of mismatch repair in eukaryotic cells, focusing on the identification of original DNA strands through nick recognition. This quiz also examines the implications of hereditary nonpolyposis colorectal cancer, particularly Lynch syndrome, highlighting the genetic mutations involved in mismatch repair proteins.

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