title: 14-3-3ζ reduces DNA damage by interacting with and stabilizing proliferating cell nuclear antigen.
abstract: Proliferating cell nuclear antigen (PCNA) is a processivity factor of DNA replication which plays critical roles in the regulation of DNA replication and repair. In this study, we show that PCNA interacts directly in vitro and in cells with 14-3-3ζ, an adaptor protein that regulates cell growth and response to DNA damage in eukaryotes. The interaction is mediated by at least two PCNA-binding sites on 14-3-3ζ, one of which is a novel non-canonical PIP (PCNA interacting protein) box. We find that DNA damages induced by UVC irradiation and MMS (methyl methanesulfonate) can enhance both the interaction of these two proteins and their co-localization with chromatin. Functional analyses suggest that 14-3-3ζ stabilizes PCNA possibly by regulating its ubiquitination, which impacts on DNA damage repair and cell viability.
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, 510632, China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Gao
authors.forename: Songsong
authors.initials: S
authors.lastname: Dan
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xie
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Qin
authors.forename: Donge
authors.initials: D
authors.lastname: Tang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
authors.forename: Langxia
authors.initials: L
authors.lastname: Liu
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D018809:Proliferating Cell Nuclear Antigen
keywords: 14-3-3ζ; DNA DAMAGE; PCNA; PROTEIN-PROTEIN INTERACTION; STABILITY