title: APC/CCdh1-dependent proteolysis of USP1 regulates the response to UV-mediated DNA damage.
abstract: Targeted protein destruction of critical cellular regulators during the G1 phase of the cell cycle is achieved by anaphase-promoting complex/cyclosome(Cdh1) (APC/C(Cdh1)), a multisubunit E3 ubiquitin ligase. Cells lacking Cdh1 have been shown to accumulate deoxyribonucleic acid (DNA) damage, suggesting that it may play a previously unrecognized role in maintaining genomic stability. The ubiquitin-specific protease 1 (USP1) is a known critical regulator of DNA repair and genomic stability. In this paper, we report that USP1 was degraded in G1 via APC/C(Cdh1). USP1 levels were kept low in G1 to provide a permissive condition for inducing proliferating cell nuclear antigen (PCNA) monoubiquitination in response to ultraviolet (UV) damage before DNA replication. Importantly, expression of a USP1 mutant that cannot be degraded via APC/C(Cdh1) inhibited PCNA monoubiquitination during G1, likely compromising the recruitment of trans-lesion synthesis polymerase to UV repair sites. Thus, we propose a role for APC/C(Cdh1) in modulating the status of PCNA monoubiquitination and UV DNA repair before S phase entry.
authors.affiliation: Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Xiomaris M
authors.initials: XM
authors.lastname: Cotto-Rios
authors.forename: Mathew J K
authors.initials: MJ
authors.lastname: Jones
authors.forename: Luca
authors.initials: L
authors.lastname: Busino
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
authors.forename: Tony T
authors.initials: TT
authors.lastname: Huang
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D015703:Antigens, CD; D029681:Arabidopsis Proteins; D015820:Cadherins / Q000378:metabolism*; D002453:Cell Cycle; D002478:Cells, Cultured; D004249:DNA Damage; D010450:Endopeptidases / Q000378:metabolism*; D016193:G1 Phase; D006367:HeLa Cells; D006801:Humans; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases; D014466:Ultraviolet Rays
chemical_list: D015703:Antigens, CD; D029681:Arabidopsis Proteins; C513384:CDH1 protein, human; D015820:Cadherins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D010450:Endopeptidases; C579228:USP1 protein, human; D064570:Ubiquitin-Specific Proteases