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Questions and Answers
What type of enzyme is responsible for synthesizing the repair patch in mismatch repair?
Which of the following types of DNA damage is repaired by base excision repair?
What is the role of DNA glycosylases in base excision repair?
Which step in base excision repair involves the removal of the deoxyribose phosphate in the backbone?
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What is the role of AP endonuclease in base excision repair?
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Which enzyme is responsible for replacing the correct nucleotide in base excision repair?
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How many DNA polymerases are encoded by human genes?
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What is the function of the MutS system in E. coli?
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What is the primary function of Nucleotide Excision Repair (NER)?
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What is the role of the nucleotide excision repairosome in NER?
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What is the result of defects in the Nucleotide Excision Repair (NER) pathway?
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What is the size of the short segment removed during NER?
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What is the final step in the Nucleotide Excision Repair (NER) pathway?
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What is the role of an exonuclease in NER?
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What is the result of the double incision step in NER?
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What is the function of the DNA polymerase in NER?
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What is the role of UvrD in DNA repair?
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Which type of DNA damage is repaired by nucleotide excision repair?
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What is the primary function of DNApol I/II in DNA repair?
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Which of the following is NOT a type of DNA repair mechanism?
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What is the outcome of homologous recombination?
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Which enzyme is involved in the proofreading activity of DNA synthesis?
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What is the role of RPA in DNA repair?
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What is the consequence of ineffective DNA repair?
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Study Notes
Cellular Mechanisms to Repair DNA Damage
- Natural polymerase error can be corrected by proofreading and mismatch repair
- Endogenous and exogenous DNA damage can be repaired by:
- Base excision repair
- Nucleotide excision repair
- Recombination (homologous and non-homologous end joining)
- Polymerase bypass
Nucleotide Excision Repair
- Recognizes bulky lesions that block DNA replication and transcription
- Requires 30 distinct proteins that function as a large complex called the nucleotide excision repairosome
- Can repair many defects corrected by direct repair, base excision, and mismatch repair
- Defects in NER underlie Xeroderma pigmentosum, Cockayne Syndrome, and Trichothiodystrophy
Steps in Nucleotide Excision Repair
- Recognition of damage by one or more protein factors
- Assembly of repair complex: nucleotide excision repairosome
- Double incision of the damaged strand by an endonuclease
- Removal of the short segment containing the damaged region by an exonuclease
- Filling in of the resulting gap by a DNA polymerase
- Ligation: a DNA ligase binds the synthesized piece into the backbone
Comparison of NER Systems in E. coli and Humans
- DNA scanning: UvrA in E. coli, XPA, XPC, and RPA in humans
- Nucleases: UvrB and UvrC in E. coli, XPF and XPG in humans
- Helicase: UvrD in E. coli, XPB and XPD in humans
- Replication system: DNA pol I/II and ligase in E. coli, DNA pol δ/ε and ligase in humans
Recombination
- DNA double-strand breaks (DSBs) are the most hazardous lesions in eukaryotic genomes
- DSBs can occur normally during DNA replication, meiosis, and immune system development
- Efficient repair of DSBs is crucial in maintaining genomic integrity and preventing tumor genesis
Homologous Recombination
- DSBs are repaired by recombination of the broken strands with their homologous sister strands during cell division
- The broken strands invade the DNA structure of the ‘good’ strands, followed by new DNA synthesis and migration of the repaired strands back out of the sister DNA
- Synthesis of the repair patch is done by a DNA polymerase
Mismatch Repair
- Example: MutS system from E. coli
- Well-known and best-characterized MMR system
Base Excision Repair
- For correction of specific chemical damage in DNA, such as:
- Uracil (deamination of cytosine or wrongly incorporated)
- Hypoxanthine (deamination of adenine)
- 3-methyladenine
- 7-methylguanosine
- 8-oxoguanine, etc.
- Requires DNA glycosylases and Apurinic/Apyrimidic (AP) endonuclease
- The DNA glycosylases are specific, such as uracil glycosylase and hypoxanthine DNA glycosylase
Steps in Base Excision Repair
- Removal of the damaged base by a DNA glycosylase
- Removal of its deoxyribose phosphate in the backbone, producing a gap: an AP site
- Replacement with the correct nucleotide by DNA polymerase beta
- Ligation of the repaired strand
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