期刊
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
卷 33, 期 2, 页码 205-211出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2011.12.002
关键词
DNA polymerase kappa (Pol kappa); Translesion DNA synthesis (TLS); Promoter; (+/-)-anti-Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)
资金
- National Natural Science Foundation of China [30770831]
- Zhejiang Provincial Natural Science Foundation for Excellent Research Groups [R207153]
- Research Foundation from the State Education Ministry of China [J20100041]
DNA polymerase kappa (Pol kappa), a member of Y-family DNA polymerases, can synthesize DNA with moderate fidelity on undamaged DNAs and replicate accurately in vitro thymine glycol, 8-oxo-G and aromatic adducts such as benzo[a]pyrene diol epoxide (BPDE). However, few studies have been done on the transcriptional regulation of Pol kappa. In this study, we predicted and cloned the promoter region of the human POLK gene. Through the analysis of deletion constructs of the POLK promoter, we demonstrated that the region -336/-141 contained repressing elements and the region -141/+226 contained positive regulatory elements for transcription of human Pol kappa. Furthermore, quantitative RT-PCR showed that human POLK mRNA expression was dysregulated in FL cells treated by BPDE. The transcriptional activities of the POLK promoter regions -336/+437 and +20/+437 were significantly reduced by BPDE treatment, indicating that transcription factors in this two regions, such as HSF1, may regulate the transcription of human POLK gene in response to BPDE. (C) 2011 Elsevier B.V. All rights reserved.
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