DNA Damage Flashcards
Transition Mutation?
PurinePurine, PyrimidinePyrimidine mutation
Transversion Mutation?
PurinePyrimidine
What are tautomeric shifts and what do they cause?
G/T: KetoEnol
A/C: AminoImino
Cause DNA replication errors (:o)
What damage does UVB cause? Wavelengths?
Cross-links adjacent C+T bases aka pyrimidine dimers (direct damage). 315-280 nm.
What damage does UVA cause? Wavelengths?
Free radicals (indirect damage). 400-315 nm.
What damage does ionizing radiation cause? What are sources?
DNA breaks. x-rays, gamma rays, cosmic rays.
What damage does thermal disruption cause?
Depurination, Single strand breaks
What damage do industrial/environmental chemicals cause?
DNA adducts, cross-linking
What does the Ames test measure?
If a substance is mutagenic (carcinogenic) based on if it mutates bacteria to use histidine.
What is the DNA repair method of last resort, and when do you use it?
Translesion synthesis, when the complementary strand/homologous chromosome is unavailable.
What does MGMT do? What is the process?
Deakylate O6-alkyl guanine (direct repair)
How is UV-induced damage corrected in bacteria? Mammals?
Photoreactivation reaction with sunlight and 4-photolyase; nucleotide excision repair
What enzymes are used in base excision repair?
Glycosidases and endonucleases
What damage does NER fix?
thymine dimers (UV) and large adducts
Defects in NER can lead to what autosomal recessive disorder?
Xeroderma Pigmentosum; hypersensitivity to sunlight
What repair process corrects replication errors? What disease is characteristic of defects in this process?
Mismatch repair; heriditary nonpolyposis colon
What response to dsDNA damage occurs in G1/S phase? What is negative about this process?
NEJ, non-homologous end-joining; can introduce mutations, cause deletions and translocations
What is required for homologous recombination? What cell cycle stage is it used?
The presence of an identical or nearly identical sequence to be used as a TEMPLATE; G2 after replication
What is defective in xeroderma pigmentosum?
NER
What genes are mutated in Li Faumeni? What are they involved in?
p53 and chk2; detection of DNA damage to prevent entry to S phase
What disease involves a Ser/Thr kinase involved in signal transduction of DNA damage signals?
Ataxia-Telogiectasia (AT)
ATM gene
What gene is mutated in Nijmegon Breakage Syndrome? What is this gene a part of?
NBS1 Gene; the MRN complex used in dsDNA break repair through homologous recombination
What is the defect in Fanconi anemia?
Inability to repair interstrand DNA cross-links
Translesional synthesis
What syndromes are caused by mutations in RECQ helicase? What is the defect?
Blooms + Werner; Hyperrecombination + defects in dsDNA break repair
What genes are implicated in breast and ovarian cancer susceptibility? What are they involved in?
BRCA1 + BRCA2; DSB repair (scaffolds)
What causes hereditary non-polyposis colorectal cancer?
Mutations in DNA mismatch repair genes
What disease is caused by mutations in the APC gene?
FAP (familial adenomatous colon cancer)
