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Some cells don't know when to stop
Date:11/19/2012

te their DNA, unwinding the strands, until the DNA strands reach a "collapse point" where they break arguably the worst kind of damage that can be done to a cell.

"We predict that this is a source of increased cancer risk in human cells that harbor checkpoint mutations," Sabatinos said. "Replication-fork instability or collapse may occur at a low frequency in these mutated cells without drug treatment, leading to more frequent DNA changes down the road."

The next step will be to determine what happens to the small fraction of mutant cells that survive this treatment.

"By bringing to bear a sophisticated combination of genetic tools, drug treatment and state-of-the-art imaging, Susan Forsburg and her co-workers have elicited a fresh perspective on a long-standing problem," said Michael Reddy, who oversees DNA replication grants at the National Institutes of Health's National Institute of General Medical Sciences, which funded the work.

"Their fundamentally revised scenario of the dynamics of fork collapse is likely to lead to invaluable insights as to how checkpoint-defective human cancer cells preserve their DNA, thereby resisting chemotherapy," he said.


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Contact: Robert Perkins
perkinsr@usc.edu
213-740-9226
University of Southern California
Source:Eurekalert

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