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Questions and Answers

What type of enzyme is responsible for synthesizing the repair patch in mismatch repair?

DNA ligase

DNA gyrase

DNA polymerase (correct)

DNA helicase

Which of the following types of DNA damage is repaired by base excision repair?

DNA cross-links

Uracil incorporation (correct)

Thymine dimers

Double-strand breaks

What is the role of DNA glycosylases in base excision repair?

To remove the damaged base (correct)

To ligate DNA strands

To synthesize new DNA strands

To repair double-strand breaks

Which step in base excision repair involves the removal of the deoxyribose phosphate in the backbone?

Removal of the deoxyribose phosphate in the backbone Signup and view all the answers

What is the role of AP endonuclease in base excision repair?

To cleave the backbone Signup and view all the answers

Which enzyme is responsible for replacing the correct nucleotide in base excision repair?

DNA polymerase beta Signup and view all the answers

How many DNA polymerases are encoded by human genes?

11 Signup and view all the answers

What is the function of the MutS system in E. coli?

Mismatch repair Signup and view all the answers

What is the primary function of Nucleotide Excision Repair (NER)?

To repair bulky lesions that block DNA replication and transcription Signup and view all the answers

What is the role of the nucleotide excision repairosome in NER?

To function as a large complex that carries out multiple steps of NER Signup and view all the answers

What is the result of defects in the Nucleotide Excision Repair (NER) pathway?

Xeroderma pigmentosum, Cockayne Syndrome, and Trichothiodystrophy Signup and view all the answers

What is the size of the short segment removed during NER?

24-32 nucleotides Signup and view all the answers

What is the final step in the Nucleotide Excision Repair (NER) pathway?

Ligation of the synthesized DNA strand Signup and view all the answers

What is the role of an exonuclease in NER?

To remove the short segment containing the damaged region Signup and view all the answers

What is the result of the double incision step in NER?

Creation of a gap in the DNA strand Signup and view all the answers

What is the function of the DNA polymerase in NER?

To synthesize DNA using the opposite strand as a template Signup and view all the answers

What is the role of UvrD in DNA repair?

Helicase activity Signup and view all the answers

Which type of DNA damage is repaired by nucleotide excision repair?

Base lesions Signup and view all the answers

What is the primary function of DNApol I/II in DNA repair?

Synthesizing new DNA strands Signup and view all the answers

Which of the following is NOT a type of DNA repair mechanism?

DNA replication Signup and view all the answers

What is the outcome of homologous recombination?

Repair of DNA double-strand breaks Signup and view all the answers

Which enzyme is involved in the proofreading activity of DNA synthesis?

DNA polymerase Signup and view all the answers

What is the role of RPA in DNA repair?

Binding to single-stranded DNA Signup and view all the answers

What is the consequence of ineffective DNA repair?

Genomic instability Signup and view all the answers

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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