Cited by 71Ubiquitin and proteasome pathwaysDNA Repair MechanismsEpigenetics and DNA Methylation

USP7 is a suppressor of PCNA ubiquitination and oxidative-stress-induced mutagenesis in human cells.

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Kashiwaba, Shu-ichiro, Kanao, Rie, Masuda, Yuji, Kusumoto-Matsuo, Rika, Hanaoka, Fumio, Masutani, Chikahide·2015·Cell Reports

Abstract

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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Crossref · 10.1016/j.celrep.2015.11.014

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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
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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