title: REV1 is important for the ATR-Chk1 DNA damage response pathway in Xenopus egg extracts.
abstract: The translesion DNA synthesis (TLS) polymerase REV1 is implicated in the bypass of the irreparable DNA damage such as interstrand crosslinks (ICLs). However, the potential role of REV1 in DNA damage response (DDR) pathway has not been determined. In this research communication, we provide evidence to demonstrate that REV1 plays a previously unidentified but important role in the ATR-Chk1 checkpoint activation in response to mitomycin C (MMC)-induced ICLs in Xenopus egg extracts. We further pinpointed that REV1 plays a downstream role of a checkpoint protein complex assembly including ATR, ATRIP, TopBP1 and the Rad9-Rad1-Hus1 complex to MMC-induced ICLs on chromatin in the DDR pathway. Notably, domain dissection analysis demonstrates that a C-terminal domain, but not the individual ubiquitin binding motifs, of REV1 is important for the binding of REV1 to MMC-damaged chromatin and the MMC-induced Chk1 phosphorylation. Yet, the ATR-Chk1 DDR pathway appears to be dispensable for the preferential association of REV1 to MMC-damaged chromatin. Taken together, REV1 is important for the DDR pathway in Xenopus egg extracts.
authors: Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors: Darla
authors: D
authors: DeStephanis
authors: Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
authors: Melissa
authors: M
authors: McLeod
authors: Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA. Electronic address: Shan.Yan@uncc.edu.
authors: Shan
authors: S
authors: Yan
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D009687:Nuclear Proteins / Q000502:physiology*; D010063:Ovum / Q000737:chemistry*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D029867:Xenopus Proteins; D014982:Xenopus laevis
chemical_list: D009687:Nuclear Proteins; D029867:Xenopus Proteins; D011494:Protein Kinases; C576898:Atr protein, Xenopus; D064007:Ataxia Telangiectasia Mutated Proteins; D000071877:Checkpoint Kinase 1; C000605875:Chek1 protein, Xenopus
keywords: ATR; Chk1; DNA damage response; REV1; TLS