TY - JOUR
T1 - Cut5 Is Required for the Binding of Atr and DNA Polymerase α to Genotoxin-damaged Chromatin
AU - Parrilla-Castellar, Edgardo R.
AU - Karnitz, Larry M.
PY - 2003/11/14
Y1 - 2003/11/14
N2 - DNA damage triggers the assembly of checkpoint signaling proteins on chromatin that activate the Chk1 signaling pathway and block S-phase progression. Here we show that genotoxin-induced Chk1 activation requires Cut5 (Mus101/TopBP1) in a process that is independent of the role of Cut5 in DNA replication. Analysis of the role of Cut5 in checkpoint activation revealed that it associated with chromatin following DNA damage in a process that required RPA. Additionally, Cut5 was required for the recruitment of Atr, DNA polymerase α, and Rad1 but not RPA to chromatin following DNA damage. Taken together, these results demonstrate that Cut5 plays an integral role in the recruitment and assembly of the Chk1 signaling cascade components following DNA damage.
AB - DNA damage triggers the assembly of checkpoint signaling proteins on chromatin that activate the Chk1 signaling pathway and block S-phase progression. Here we show that genotoxin-induced Chk1 activation requires Cut5 (Mus101/TopBP1) in a process that is independent of the role of Cut5 in DNA replication. Analysis of the role of Cut5 in checkpoint activation revealed that it associated with chromatin following DNA damage in a process that required RPA. Additionally, Cut5 was required for the recruitment of Atr, DNA polymerase α, and Rad1 but not RPA to chromatin following DNA damage. Taken together, these results demonstrate that Cut5 plays an integral role in the recruitment and assembly of the Chk1 signaling cascade components following DNA damage.
UR - http://www.scopus.com/inward/record.url?scp=0242413125&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0242413125&partnerID=8YFLogxK
U2 - 10.1074/jbc.C300418200
DO - 10.1074/jbc.C300418200
M3 - Article
C2 - 14525986
AN - SCOPUS:0242413125
SN - 0021-9258
VL - 278
SP - 45507
EP - 45511
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -