title: CHFR is important for the first wave of ubiquitination at DNA damage sites.
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.
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Jiaxue
authors.initials: J
authors.lastname: Wu
authors.forename: Sharad C
authors.initials: SC
authors.lastname: Paudyal
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: You
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D007834:Lasers; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D025521:Tumor Suppressor Proteins; D011064:Poly Adenosine Diphosphate Ribose; C412002:CHFR protein, human; C558788:CHFR protein, mouse; D044767:Ubiquitin-Protein Ligases; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases