Ubiquitin Protein Ligase Ring2 Is Involved in S-phase Checkpoint and DNA Damage in Cells Exposed to Benzo[a]pyrene.
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.
Department of Occupational Health, School of Public Health, Shanxi Medical University, 030001, Taiyuan, People's Republic of China. yj750410@163.com.
Jin
J
Yang
Department of Occupational Health, School of Public Health, Shanxi Medical University, 030001, Taiyuan, People's Republic of China.
Wentao
W
Chen
Department of Occupational Health, School of Public Health, Shanxi Medical University, 030001, Taiyuan, People's Republic of China.
Yanfeng
Y
Fan
Department of Occupational Health, School of Public Health, Shanxi Medical University, 030001, Taiyuan, People's Republic of China.
Huitao
H
Zhang
Department of Occupational Health, School of Public Health, Shanxi Medical University, 030001, Taiyuan, People's Republic of China.
Wubin
W
Wang
Department of Occupational Health, School of Public Health, Shanxi Medical University, 030001, Taiyuan, People's Republic of China.
Hongjie
H
Zhang
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001980:Bronchi; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018736:DNA Adducts / Q000494:pharmacology*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
C400134:BAP1 protein, human; D018736:DNA Adducts; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D043222:Ubiquitin Thiolesterase
Benzo[a]pyrene; Cell cycle; DNA damage; Ubiquitin protein ligase