Transcription is a cellular process by which genetic information from DNA is copied to messenger RNA for protein production. But anticancer drugs and environmental chemicals can sometimes interrupt this flow of genetic information by causing modifications in DNA.
Chemists at the University of California, Riverside have now developed a test in the lab to examine how such DNA modifications lead to aberrant transcription and ultimately a disruption in protein synthesis.
The chemists report that the method, called "competitive transcription and adduct bypass" or CTAB, can help explain how DNA damage arising from anticancer drugs and environmental chemicals leads to cancer development.
"Aberrant transcription induced by DNA modifications has been proposed as one of the principal inducers of cancer and many other human diseases," said Yinsheng Wang, a professor of chemistry, whose lab led the research. "CTAB can help us quantitatively determine how a DNA modification diminishes the rate and fidelity of transcription in cells. These are useful to know because they affect how accurately protein is synthesized. In other words, CTAB allows us to assess how DNA damage ultimately impedes protein synthesis, how it induces mutant proteins. "
Study results appeared online in Nature Chemical Biology on Aug. 19.
Wang explained that the CTAB method can be used also to examine various proteins involved in the repair of DNA. One of his research group's goals is to understand how DNA damage is repaired -- knowledge that could result in the development of new and more effective drugs for cancer treatment.
"This, however, will take more years of research," Wang cautioned.
His lab has a long-standing interest in understanding the biological and human health consequences of DNA damage. The current research was supported by the National Cancer Institute, the National Institute of Environmental Health Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
Wang was joined in the research by UC Riverside's Changjun You (a postdoctoral scholar and the research paper's first author), Xiaoxia Dai, Bifeng Yuan, Jin Wang and Jianshuang Wang; Philip J. Brooks of the National Institute on Alcohol Abuse and Alcoholism, Md.; and Laura J. Niedernhofer of the University of Pittsburgh School of Medicine, Penn.
Next, the researchers plan to use CTAB to investigate how other types of DNA modifications compromise transcription and how they are repaired in human cells.
- Changjun You, Xiaoxia Dai, Bifeng Yuan, Jin Wang, Jianshuang Wang, Philip J Brooks, Laura J Niedernhofer, Yinsheng Wang. A quantitative assay for assessing the effects of DNA lesions on transcription. Nature Chemical Biology, 2012; DOI: 10.1038/nchembio.1046
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