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
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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,
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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
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4
Q

ATR activation

A
  • ssDNA = trigger
  • Experiment = look at RPA + ATR nuclei foci when DNA damage
  • Knockdown
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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
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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
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