MCGB - Errors In DNA Replication and Cancer Flashcards
Give three things that may cause DNA replication stress to arise.
Replication machinery has a defect (eg helicase stalls), factors hinder replication fork progression, defects in response pathways
What is “slippage”?
This occurs when there is a repeat of three nucleotides, and one is missed out, forming a loop. This can cause a base to be either omitted or added.
What causes nucleotide misincorporation?
Defects in 3’ to 5’ exonuclease.
What are the consequences of a double strand break in DNA?
Genomic mutations (cancer) and cell growth inhibition (ageing)
Give an example of a trinucleotide repeat disorder.
Huntington’s.
Give an example of a progeroid syndrome
Werner syndrome
Give some exogenous causes of DNA damage.
Ionising radiation, alkylating agents, UV light, anti-cancer agents.
Give some endogenous sources of DN damage.
DNA replication errors, VDJ recombination, free radicals.
What is a checkpoint in the cell cycle?
A temporary arrest which provides time for DNA damage to be repaired.
What is senescence?
Permanent cell cycle arrest.
Give som examples of different DNA repair pathways.
Base excision repair, mismatch repair, nucleotide excision repair.
How does non-homologous end joining repair a double strand break?
Recruit proteins to end of DNA to form a complex, use DNA ligase to join broken ends back together.
How does homology-directed repair lead to double strand break repair?
DNA is resected, homologous template (preferably sister chromatid) used to reform.
Give some sub-pathways of homology-directed repair.
Single strand annealing, synthesis-dependent strand annealing, double-strand break repair.
Give some examples of conditions caused by a defect in DNA mismatch repair.
Lynch syndrome and colorectal cancer.
