DNA Damage Response Flashcards
during replication, a lesion occurs, DNA polymerase cannot continue
Fork reversal occurs, fixing strand with the ssDNA repair pathway
for stabilization during fork reversal
RPA (ss binding protein)
9-1-1 complex (trimeric clamp)
special clamp loader
PCNA is a
homotrimer, 3 parts, all the same
9-1-1 is a
heterotrimer,
3 parts, all different
named for 3 yeast genes, RAD9-RAD1-HUS1
PCNA is loaded by
pentameric clamp loader
RFC1-5
clamp loader for 9-1-1 complex
has 4 subunits
plus fifth one called Rad17
9-1-1 clamp loader finds
ds-ss junction with 5’ open end
presence of 9-1-1 and RPA coated ss
sends a signal to protein kinase ATR
ATR binds to
ATRIP, which connects to RPA
ATR phosphorylates Chk1, which stops DNA replication
For double-stranded breaks,
H2AX histone, has SQ in tail
S becomes phosphorylated upon ds break
phosphorylation occurs for a long distance from the break
phosphorylated H2AX is called
gammaH2AX
after H2AX is phosphorylated
bridge is built connecting broken ends
MRN complex
held together by Zn
p53 has 3 important roles
transcription factor, promotes the expression of genes that alter the cell
controls whether the cell will arrest the cell cycle or go into apoptosis
tumor suppressor gene, found mutated in half of all solid tumors
genes that promote the growth of tumor cells
oncogenes
p53 acts as transcription factor for
p21, an inhibitor protein
stops DNA replication
