Biochemistry: DNA Repair Mechanisms and Clinical Implications

What is the primary function of DNA polymerase III during DNA replication?

It performs proofreading to correct the majority of mutations that arise during DNA replication.

What is the uvrABC system responsible for?

It is involved in the removal of pyrimidine dimers from DNA.

How does DNA photolyase function?

It repairs DNA by using light energy to cleave pyrimidine dimers.

How does a cell recognize the older strand of double-stranded DNA?

The older strand is marked by methylation, specifically by Dam methylase in GAMTC sequences.

What role does Uracil-DNA glycosidase play in DNA repair?

It removes uracil produced by the deamination of cytosine.

What is the SOS response in DNA repair?

It is a cellular response to DNA damage that activates repair mechanisms and is crucial for survival under stress.

What general role does recombination play in DNA repair?

Recombination helps repair DNA by allowing the exchange of genetic information between DNA molecules.

What are the main types of DNA repair systems active in cells?

Base-excision repair, mismatch repair, and nucleotide-excision repair.

What percentage of DNA damage is repaired by DNA repair machinery?

It takes care of 99.99% of damage to DNA.

What is the significance of the 2015 Chemistry Nobel Prize in relation to DNA repair?

It was awarded to Tomas Lindahl, Paul Modrich, and Aziz Sancar for their contributions to understanding DNA repair mechanisms.

What proteins are involved in mismatch repair in E. coli?

Dam methylase, MutH, MutL, MutS proteins, DNA helicase II, SSB, DNA polymerase III, and DNA ligase.

What type of damage does base-excision repair target?

It targets abnormal bases, such as uracil, hypoxanthine, and alkylated bases.

What type of damage does nucleotide-excision repair address?

It repairs DNA lesions that cause large structural changes, such as pyrimidine dimers.

What is the role of DNA ligase in DNA repair?

DNA ligase joins newly synthesized DNA pieces to the original DNA strand.

What is the mechanism of action for mismatch repair?

MutS binds to the mismatch, MutH makes a nick in the DNA, and exonucleases remove the mismatched base before DNA polymerase III and ligase complete the repair.

What is the clinical significance of hereditary non-polyposis colorectal cancer (HNPCC)?

It is caused by defective human analogs of mutL and mutS, leading to an increased risk of colorectal cancer.

What are the major clinical features of Cockayne syndrome?

Dwarfism, premature aging, pigmentary retinal degeneration, optic atrophy, deafness, and sensitivity to sunlight.

What is the function of DNA glycosylases in base-excision repair?

They recognize damaged bases and cleave the glycosyl bond, creating an AP site for further repair.

What is the role of AP endonucleases in DNA repair?

They act on AP sites created by the removal of damaged bases to initiate further repair processes.

What type of mutation does the Bloom syndrome gene (RecQ3) affect?

It is involved in unwinding DNA to allow repair to occur.

What is an AP site in DNA?

An AP (apurinic/apyrimidinic) site is a location in DNA that has lost a purine or pyrimidine base, often created by glycosylases.

What is the role of Uracil glycosylase?

Uracil glycosylase specifically recognizes and removes uracil from DNA, creating an AP site.

What is the function of DNA polymerase I and ligase in DNA repair?

DNA polymerase I fills in the gaps left after the removal of damaged bases, while ligase seals the nicks in the DNA backbone.

What is Nucleotide Excision Repair (NER)?

NER is a DNA repair mechanism that removes bulky DNA lesions, such as pyrimidine dimers, and is initiated by ABC excinuclease.

What is Xeroderma pigmentosa?

Xeroderma pigmentosa is a genetic disorder caused by defective nucleotide excision repair, leading to photosensitivity and increased skin cancer risk.

What is the role of DNA photolyases?

DNA photolyases repair cyclobutane pyrimidine dimers by binding to the dimers and using light energy to break the bonds.

What does 06-Methylguanine DNA methyltransferase do?

It transfers a methyl group to a specific cysteine residue, repairing 06-methylguanine lesions in DNA.

What is the S.O.S. Response in DNA repair?

The S.O.S. Response is a mechanism activated in response to extensive DNA damage, allowing for error-prone repair to maintain cell survival.

What triggers the activation of RecA in the S.O.S. Response?

RecA is activated when it binds to single-stranded DNA (ssDNA), leading to the degradation of the LexA repressor.

What is Transcription-Coupled Repair?

Transcription-Coupled Repair is a process where actively transcribed DNA is repaired more quickly, utilizing stalled RNA polymerase as a signal.

How does the tumor suppressor p53 relate to DNA damage?

p53 monitors DNA damage and can induce apoptosis if the damage is too extensive, inhibiting recombination in cases of excessive mismatch.

What are the two pathways to fix Double Strand Breaks (DSBs)?

The two pathways are recombination and end joining.

What is the role of Rad51 in DNA repair?

Rad51 is involved in homologous recombination, facilitating strand invasion and joint molecule formation during DSB repair.

What is the function of Ku 70/80 in DNA repair?

Ku 70/80 heterodimer is involved in the non-homologous end joining pathway, recognizing and binding to DSBs.

What is the significance of the BRCA1 gene?

BRCA1 is involved in transcription-coupled repair and interacts with RAD51 to facilitate DNA repair processes.

What are the consequences of defective nucleotide excision repair?

Defective nucleotide excision repair can lead to diseases like Xeroderma pigmentosa, characterized by skin lesions and cancer.

What is the role of helicase in Nucleotide Excision Repair?

Helicase displaces the damaged DNA strand after excision, allowing for repair synthesis.

What is the difference between intrinsic and extrinsic apoptosis?

Intrinsic apoptosis is triggered by DNA damage, while extrinsic apoptosis is initiated by extracellular signals acting on membrane receptors.

What are the key components involved in the intrinsic pathway of apoptosis?

Key components include p53, Bcl-2, and caspases, which mediate the apoptotic process.

What is the role of IAPs in apoptosis?

Inhibitor of Apoptosis Proteins (IAPs) prevent apoptosis by inhibiting caspases.

What is the process of strand invasion in DSB repair?

Strand invasion involves the pairing of a single strand of DNA with a homologous double-stranded DNA to facilitate repair.

What is the role of mismatch repair in DNA repair?

Mismatch repair corrects errors that occur during DNA replication, ensuring genomic stability.

What is the function of DNA ligase in DNA repair?

DNA ligase seals nicks in the DNA backbone, completing the repair process.