CHFR is important for the first wave of ubiquitination at DNA damage sites

Chao Liu, Jiaxue Wu, Sharad C. Paudyal, Zhongsheng You, Xiaochun Yu

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1698-1710
Number of pages13
JournalNucleic acids research
Volume41
Issue number3
DOIs
StatePublished - Feb 2013

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