Chromosome biology lecture 12 Flashcards
1
Q
SOS response (E coli)
A
- Surveillance mechanisms that monitor structure of chromosome
- Coord LexA transcriptional repressor + DNA repair protein RecA
- ssdNA damage repaired w/ HR, recognised by RecA which initiates strand invasion
- RecA interacts w/ LexA by reliving repressor activity of LexA → transcribe SOS box genes
2
Q
DNA damage cell cycle signalling (All)
A
- Experiment show deletion of checkpoint genes → loss of cell cycle arrest
- Checkpoints ensure DNA replicated only once
- Chk1 (ATR) + Chk2 (ATM)
- Activated Chk2 phosph Cdc25 which degrades Cdk2/cyclinE via p53 via p21
- Chk1 phosph + inhibits Cdc7 needed for replication origin firing, also inhibits activation of Cdc25
- AT = chromosome instability, ATM kinase,
3
Q
MRN as sensor of DNA damage
A
- MRN assoc w/ DNA damage
- 3’-5’ exonuclease property
- Mutations → ATLD/NBS, patients are sensitive to IR
- Nbs1 reacts w/ ATM through conserved CTD, Nbs1 binds ds break
- Active ATM = auto-phosph + forms dimer
4
Q
ATR activation
A
- ssDNA = trigger
- Experiment = look at RPA + ATR nuclei foci when DNA damage
- Knockdown
5
Q
911 complex
A
- Identified in genetic screen yeast
- Similar to PCNA, ring-like structure
- Rad17 + 911 thought to load DNA damage sensing complex onto chromatin
6
Q
Tobp1
A
- ATR + Rad17/911 needed for Chk1 phosph but recruited independently of each other to ssDNA
- Reduction of TOPB1 in mammals → ↓ phosph of Chk1 + other ATR substrates
- 8 BRCT phospho-reogn motifs
- TOBP1 = ATR activation domain, recruited by 911
