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.

A quantitative assay for assessing the effects of DNA lesions on transcription

Source: University of California, Riverside