ATR Prevents Division of Cells with Damaged DNA

The study appeared in the February 19, 2002, online edition of Genes and Development.

ATR and the similar ATM protein have previously been shown to be involved in the response to DNA damage. However, earlier experiments to determine the role of ATR in preventing cells with damaged DNA from dividing have been contradictory and the precise roles of these proteins have remained obscure.

In the current study, investigators from the California Institute of Technology (Caltech, Pasadena, USA; www.caltech.edu) utilized a novel mouse model to produce cells lacking the ATR kinase. After exposure to ionizing radiation, the ATR deficient cells were found to have major defects in cell-cycle checkpoint regulation and halting of the cell cycle. These mouse cells proceeded dangerously through the cell division cycle with chromosome breaks, demonstrating a role for ATR in maintaining the integrity of DNA.

"It is a very exciting time for the DNA damage response field. Everywhere you look in these pathways, connections can be made to how cancer is normally prevented by maintaining the integrity of the genome. Subtle, yet-to-be-determined deficiencies in any of a number of these DNA damage response molecules may broadly influence cancer risk in humans,” explained first author Dr. Eric J. Brown, a researcher at Caltech.



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