DNA Damage Repair Mechanisms

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Questions and Answers

Which process is primarily involved in repairing extensive DNA damage when all replication forks are blocked?

Base Excision Repair

Error prone translesion DNA synthesis (correct)

Nucleotide Excision Repair

Mismatch Repair

What is a characteristic feature of the bacterial DNA polymerases IV and V during the SOS response?

They are part of the nucleotide excision repair pathway.

They replicate DNA accurately without error.

They have high fidelity and proofreading abilities.

They lack proofreading exonuclease activity. (correct)

In which condition is the SOS response activated to facilitate DNA repair mechanisms?

Presence of low mutation rates

Lack of base pair mismatches

Significant DNA damage leading to blocked replication forks (correct)

Normal cell cycle progression

Which of the following is true regarding the UmuD’ and UmuC complex in translesion DNA synthesis?

It allows DNA polymerase to replicate through lesions. Signup and view all the answers

In the context of hereditary non-polyposis colorectal cancer (HNPCC), which repair mechanism is most relevant to the review of DNA damage and repair?

Mismatch Repair Signup and view all the answers

What is the main genetic defect associated with Xeroderma pigmentosum?

Mutations in the Nucleotide Excision Repair system Signup and view all the answers

Which proteins are primarily involved in the mismatch repair defects associated with HNPCC?

hMLH1 and hMSH2 Signup and view all the answers

What kind of mutations does O6-methylguanine primarily cause during DNA replication?

G-C to A-T mutations Signup and view all the answers

Which process directly repairs pyrimidine dimers without excising nucleotides?

Photoreactivation Signup and view all the answers

What is the main function of the AlkB proteins in DNA repair?

Oxidative demethylation of alkylated nucleotides Signup and view all the answers

In which wavelength range do photolyases absorb light to facilitate DNA repair?

350-500 nm Signup and view all the answers

What are the products formed during the oxidative demethylation process by AlkB?

Formaldehyde, CO2, and succinate Signup and view all the answers

Which condition is NOT a symptom of hereditary non-polyposis colorectal cancer (HNPCC)?

Skin lesions Signup and view all the answers

Which of the following is a characteristic of Nucleotide Excision Repair?

It involves dual incision for bulky lesions. Signup and view all the answers

What is the primary function of the enzymes MLH1 and PMS1 in eukaryotic mismatch repair?

To stabilize MSH complexes and bind to DNA. Signup and view all the answers

Which type of DNA damage is primarily repaired by Base-Excision Repair mechanisms?

Deamination of cytosine resulting in uracil incorporation. Signup and view all the answers

How does the SOS response in DNA repair mainly function?

By inducing global transcriptional changes to enhance repair mechanisms. Signup and view all the answers

Which enzyme is involved in the removal of uracil from DNA during the base-excision repair process?

Uracil DNA glycosylase. Signup and view all the answers

What type of DNA lesions are primarily addressed by the Nucleotide Excision Repair pathway?

Pyrimidine dimers formed from UV light exposure. Signup and view all the answers

What distinguishes hereditary non-polyposis colorectal cancer (HNPCC) in relation to mismatch repair?

It is characterized by mutations in the MSH2 and MSH6 genes. Signup and view all the answers

What is the role of the UvrA, UvrB, and UvrC subunits in Nucleotide Excision Repair?

To recognize and incise DNA at bulky lesions. Signup and view all the answers

Study Notes

### Replication Fork Interaction with DNA Damage

When a replication fork encounters DNA damage, repair mechanisms are activated to restore DNA integrity.
The cell cycle is arrested to allow for repair.
Homologous recombination is frequently employed in repairing damaged DNA, utilizing information from sister chromatids or homologous chromosomes.

### SOS Response

The SOS response is a bacterial cellular response to DNA damage.
It involves the activation of a set of genes, including those for DNA repair and other protective functions.
It triggers the synthesis of DNA polymerase IV and V, which are error-prone translesion DNA synthesis (TLS) polymerases involved in bypassing damaged DNA sequences.

### Mismatch Repair

Mismatch repair corrects errors introduced during DNA replication.
It involves recognizing and removing mismatched bases from newly synthesized DNA strands.
In bacteria, the system involves MutH, MutL, and MutS proteins.
Key proteins in eukaryotic mismatch repair include MSH2, MSH3, MSH6, MLH1, and PMS1.

### Base Excision Repair

Repairs damage caused by environmental agents.
It involves removing damaged bases by cleaving the N-glycosyl bond between the base and the sugar of the DNA backbone.
This creates an abasic site (AP site).
Uracil DNA glycosylases remove uracil from DNA, which arises from cytosine deamination.

### Nucleotide Excision Repair

Removes bulky lesions and pyrimidine dimers from DNA.
The system involves three subunits: UvrA, UvrB, and UvrC.
It involves two specific endonucleolytic cleavages to remove the damaged DNA segment.

### Xeroderma Pigmentosum

A rare genetic disease characterized by sun sensitivity, increased risk of skin cancer, and neurological abnormalities.
It results from mutations in genes involved in nucleotide excision repair, specifically XPA to XPG.
This inability to repair pyrimidine dimers leads to the accumulation of DNA damage, increasing the risk of cancer.

### Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

An autosomal dominant inherited disease caused by defects in mismatch repair.
Mutations in genes such as hMLH1 and hMSH2 are common in HNPCC.
The condition increases the risk of colorectal cancer and other malignancies.

### Direct Repair

Repair mechanism that does not involve excising or removing a base or a nucleotide.

### Photoreactivation

A direct repair mechanism that uses light energy to reverse DNA damage.
DNA photolyases, encoded by phr genes, recognize and bind to pyrimidine dimers.
Upon exposure to blue light, photolyases break apart the dimer, restoring the original DNA sequence.

### Alkylation Repair

Removes alkyl groups from DNA bases.
Methylguanine methyltransferase (MGMT) directly removes methyl groups from O6-methylguanine, restoring the original guanine base.
AlkB proteins can demethylate alkylated bases by oxidative decarboxylation.
Human AlkB homologs include ALKBH1 to ALKBH8 and FTO, suggesting a role in removing various alkylated bases in humans.

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Description

This quiz covers key mechanisms of DNA damage repair, including the replication fork's response to DNA damage, the SOS response in bacteria, and mismatch repair processes. Test your understanding of how cells interact with DNA damage and the strategies employed for accurate repair.