APC/CCdh1-dependent proteolysis of USP1 regulates the response to UV-mediated DNA damage.
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.
Mesh Terms:
Anaphase-Promoting Complex-Cyclosome, Arabidopsis Proteins, Cadherins, Cell Cycle, Cells, Cultured, DNA Damage, Endopeptidases, G1 Phase, HeLa Cells, Humans, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Specific Proteases, Ultraviolet Rays
Anaphase-Promoting Complex-Cyclosome, Arabidopsis Proteins, Cadherins, Cell Cycle, Cells, Cultured, DNA Damage, Endopeptidases, G1 Phase, HeLa Cells, Humans, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Specific Proteases, Ultraviolet Rays
J. Cell Biol.
Date: Jul. 25, 2011
PubMed ID: 21768287
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