DNA damage and repair Flashcards
(27 cards)
Why is DNA more prone to attack compared to RNA?
DNA has a stable phosphodiester backbone but a less stable sugar-base glycosyl bond, making it more prone to base loss.
Name two categories of DNA damage sources.
External (e.g., UV, chemicals) and endogenous (e.g., ROS, replication errors).
What are the main types of chemical DNA damage?
Oxidation, hydrolysis, methylation, deamination.
What is the consequence of failure to repair deaminated DNA bases?
Point mutations.
What is the long-term result of unrepaired DNA damage?
Mutations, deletions, insertions, translocations, cancer, aging.
How do thymine dimers affect DNA?
They cause a kink that blocks DNA polymerase, potentially causing deletions.
Give an example of a chemical mutagen and its effect.
Aflatoxin (after P450 activation) binds guanine and distorts the helix.
What are the four main types of DNA repair?
Direct reversal, excision repair, double-strand break repair, and damage tolerance.
What enzymes are involved in direct repair of thymine dimers?
Photolyase (not present in placental mammals).
What enzyme removes aberrant methyl groups in direct repair?
Methyltransferase (e.g., O6-methylguanine methyltransferase).
What are the three types of excision repair?
Base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR).
What initiates BER?
DNA glycosylases that recognize specific base damage.
What does nucleotide excision repair remove?
Bulky lesions like pyrimidine dimers and oxidative damage.
What distinguishes GGR from TCR in NER?
GGR repairs the whole genome; TCR targets actively transcribed strands.
What causes mismatched base pairs?
DNA replication errors and homologous recombination mismatches.
What protein recognizes mismatches in E. coli?
MutS.
How does strand discrimination work in E. coli MMR?
Methylation at GATC sites by Dam methylase.
What causes HNPCC (Lynch syndrome)?
Defects in MMR genes like MSH2, MLH1.
What are the two main pathways for DSB repair?
Homologous recombination (HR) and non-homologous end-joining (NHEJ).
What protein complex initiates NHEJ?
Ku70/80 binds DNA ends and recruits DNA-PKcs.
What is the key feature of homologous recombination?
Strand invasion and formation of Holliday junctions.
What is translesion DNA synthesis?
Specialized polymerases bypass DNA lesions to allow replication to continue.
Which polymerase is associated with XPV?
Pol eta, which inserts A across from TT dimers.
What is Xeroderma Pigmentosum (XP)?
A cancer-prone syndrome caused by defective NER, resulting in UV sensitivity.
