DNA Repair: Discovery of a Process with Critical Implications for Cancer Treatment
November 13, 2008 – In a study published in the Proceedings of the National Academy of Sciences of the USA (PNAS), Dr Elliot Drobetsky and Dr El Bachir Affar explain how they discovered, along with other research investigators, a new biomedical pathway that controls one of the DNA repair systems. Ultimately this discovery could help reverse the effects of such carcinogenic agents as ultraviolet light and cigarette smoke on DNA as well as prevent tumour development with greater effectiveness.
“Our study is the first to identify a regulatory role of the ATR protein in a specific DNA repair system called nucleotide excision repair(NER),” explains Elliot Drobetsky, the study’s lead author. “NER removes parts of damaged DNA before they destroy the function of tumour-preventing proteins in the body.”
Characterizing how the NER system is turned on and off is critical to understanding how tumours develop. The research team used cultured lung cells to study the role of ATR. They discovered that inhibiting ATR resulted in a dysfunctional NER system during a specific critical period in the cell growth cycle.
Further to this, they also found that the ATR-mediated repair system was completely deficient in some tumour cell lines, providing solid evidence that this DNA repair function may be crucial in cancer development. “Our study reveals an original mechanism that explains how exposure to environmental carcinogens provokes and fosters cancer growth,” adds Dr Drobetsky.
Implications for Chemotherapy
This discovery could have implications for treating cancer with chemotherapy. It is believed that tumours showing a defective ATR-mediated repair system are expected to respond extremely well to chemotherapy because their cells, unlike normal cells in the rest of the body, would be extremely hypersensitive to certain chemotherapeutic agents.
“Our study opens an entirely new area of research,” states Dr Drobetsky. “Our findings are of critical importance not only for understanding how cancer develops but also for devising new strategies that could considerably improve cancer treatment.”
About the Study:
The study, ATR Kinase Is Required for Global-Genomic Nucleotide Excision Repair Exclusively During S Phase in Human Cells , published on the Proceedings of the National Academy of Sciences of the USA (PNAS) web site, is the fruit of a collaboration between Yannick Auclair, Raphaël Rouget, El Bachir Affar and Elliot A. Drobetsky of the Maisonneuve-Rosemont Hospital Research Centre and the University of Montreal.