USP7 is a suppressor of PCNA ubiquitination and oxidative-stress-induced mutagenesis in human cells.
Open accessAbstract
Mono-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.
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This defect seems due to a role of USP7 in regulating ubiquitination of the PCNA sliding clamp.
“This defect seems due to a role of USP7 in regulating ubiquitination of the PCNA sliding clamp (Kashiwaba et al., 2015; Qian et al., 2015; Masuda et al., 2019).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Kashiwaba et al., 2015
USP7 deubiquitinates PCNA during interphase to suppress PCNA monoubiquitination in response to oxidative and, to a lesser extent, UV-induced DNA damage.
“Most directly, USP7 has been reported to deubiquitinate PCNA during interphase of the cell cycle, to suppress PCNA monoubiquitination in response to oxidative – and to a lesser extent, UV-induced – DNA damage (Kashiwaba et al., 2015).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Kashiwaba et al., 2015
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References 39 · Cited by 71
- Authors
- Kashiwaba, S.-I., Kanao, R., Masuda, Y., Kusumoto-Matsuo, R., Hanaoka, F., & Masutani, C.
- Affiliations
- Research Institute of Environmental Medicine, Nagoya University (JP)
- Gakushuin University (JP)
- Corresponding author
- Masutani, Chikahide
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 13
- Issue
- 10
- Pages
- 2072-2080
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2195280029
- Cited by
- 71
- References
- 39
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 6 · 2020: 12 · 2019: 8 · 2018: 2 · 2017: 9 · 2016: 6
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (25241011, 15K14953, 26740017)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- USP7, USP1, PCNA, monoubiquitination, deubiquitinase, oxidative stress, UV mutagenesis, DNA replication, DNA repair, error-prone DNA polymerases, S phase, cell cycle
- MeSH terms
- Ubiquitin-Specific Peptidase 7, Cell Line, DNA Damage, Flow Cytometry, Humans, Hydrogen Peroxide, Transfection, Polymerase Chain Reaction, Mutagenesis, Mutagenesis, Site-Directed, Oxidative Stress, Proliferating Cell Nuclear Antigen, RNA, Small Interfering, Ubiquitin Thiolesterase, Ubiquitination
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