| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2040635 | Cell Reports | 2015 | 9 Pages |
•USP7 deubiquitinates mono-ubiquitinated PCNA in vitro•USP7 suppresses UV- and oxidative-stress-induced PCNA mono-ubiquitination in cells•USP1 acts in S-phase, whereas USP7 acts throughout interphase•USP1 and USP7 suppress UV- and H2O2-induced mutagenesis, respectively
SummaryMono-ubiquitinated PCNA activates error-prone DNA polymerases; therefore, strict regulation of PCNA mono-ubiquitination is crucial in avoiding undesired mutagenesis. In this study, we used an in vitro assay system to identify USP7 as a deubiquitinating enzyme of mono-ubiquitinated PCNA. Suppression of USP1, a previously identified PCNA deubiquitinase, or USP7 increased UV- and H2O2-induced PCNA mono-ubiquitination in a distinct and additive manner, suggesting that USP1 and USP7 make different contributions to PCNA deubiquitination in human cells. Cell-cycle-synchronization analyses revealed that USP7 suppression increased H2O2-induced PCNA ubiquitination throughout interphase, whereas USP1 suppression specifically increased ubiquitination in S-phase cells. UV-induced mutagenesis was elevated in USP1-suppressed cells, whereas H2O2-induced mutagenesis was elevated in USP7-suppressed cells. These results suggest that USP1 suppresses UV-induced mutations produced in a manner involving DNA replication, whereas USP7 suppresses H2O2-induced mutagenesis involving cell-cycle-independent processes such as DNA repair.
Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide
