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Ubiquitin Protein Ligase Ring2 Is Involved in S‐phase Checkpoint and DNA Damage in Cells Exposed to Benzo[ a ]pyrene
Author(s) -
Yang Jin,
Chen Wentao,
Fan Yanfeng,
Zhang Huitao,
Wang Wubin,
Zhang Hongjie
Publication year - 2016
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21811
Subject(s) - benzo(a)pyrene , ubiquitin ligase , ubiquitin , chemistry , g2 m dna damage checkpoint , dna damage , microbiology and biotechnology , dna ligase , ddb1 , dna , carcinogen , biochemistry , cell cycle checkpoint , biology , cell cycle , gene
ABSTRACT Previous studies in our laboratory demonstrated that Ring2 may affect DNA damage and repair through pathways other than through regulating the expression of the nucleotide excision repair protein. In a series of experiments using wild‐type cell (16HBE and WI38) and small interfering RNA (siRNA) Ring2 cells exposed to benzo[ a ]pyrene (BaP), we evaluated the cell cycle and DNA damage. The benzo(a)pyrene‐7,8‐dihydrodiol‐9,10‐epoxide (BPDE–DNA) adduct assay demonstrated that in vitro exposure to BaP increased DNA damage in a time‐ and dose‐dependent manner in wild‐type and siRNA Ring2 cells. Analysis of covariance showed that a decrease of Ring2 caused DNA hypersensitivity to BaP. Flow cytometry results and proliferating cell nuclear antigen levels indicated that inhibition of Ring2 attenuated the effect of BaP on S‐phase arrest. Taken together, these data implied that the lower proportion of cells in the S phase induced by inhibition of Ring2 may play an important role in DNA hypersensitivity to BaP.