TY - JOUR
T1 - CHFR is important for the first wave of ubiquitination at DNA damage sites
AU - Liu, Chao
AU - Wu, Jiaxue
AU - Paudyal, Sharad C.
AU - You, Zhongsheng
AU - Yu, Xiaochun
N1 - Funding Information:
The American Cancer Society [IRG-58-010-52 to Z.Y.]; the National Institute of Health (NIH) [GM098535 to Z.Y., CA132755 and CA130899 to X.Y.] and a Siteman Career Award in Breast Cancer Research (to Z.Y.). Recipient of the Era of Hope Scholar Award from the Department of Defense (to X.Y.). Funding for open access charge: NIH [R01CA130899].
PY - 2013/2
Y1 - 2013/2
N2 - Protein ubiquitination plays an important role in activating the DNA damage response and maintaining genomic stability. In response to DNA double-strand breaks (DSBs), a ubiquitination cascade occurs at DNA lesions. Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). At DSBs, CHFR regulates the first wave of protein ubiquitination. Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Thus, these results demonstrate that CHFR is an important E3 ligase in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation.
AB - Protein ubiquitination plays an important role in activating the DNA damage response and maintaining genomic stability. In response to DNA double-strand breaks (DSBs), a ubiquitination cascade occurs at DNA lesions. Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). At DSBs, CHFR regulates the first wave of protein ubiquitination. Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Thus, these results demonstrate that CHFR is an important E3 ligase in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation.
UR - http://www.scopus.com/inward/record.url?scp=84873631924&partnerID=8YFLogxK
U2 - 10.1093/nar/gks1278
DO - 10.1093/nar/gks1278
M3 - Article
C2 - 23268447
AN - SCOPUS:84873631924
SN - 0305-1048
VL - 41
SP - 1698
EP - 1710
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 3
ER -