Analysis reveals extent of DNA repair army

Cells have the remarkable ability to keep track of their genetic contents and -- when things go wrong to step in and repair the damage before cancer or another life-threatening condition develops.

But precisely how cells monitor the integrity of their genomes, identify problems, and intervene to repair broken or miscoded DNA has been one of nature's closely held secrets. Now, however, a report in the journal Science describes a new database developed by a team of researchers from the Howard Hughes Medical Institute at Harvard Medical School that is providing the first detailed portrait of the army of more than 700 proteins that helps maintain DNAs integrity.

"The generation of this database is changing the way we think about the DNA damage response," explained HHMI investigator Stephen J. Elledge of Harvard, the senior author of the new study published on May 25, 2007, in Science. "Our work paints a broader landscape of this critical response that helps cells keep their genomes intact."

The DNA damage response is a routine event in the life of any cell. Stress caused by environmental factors such as exposure to ultraviolet light, ionizing radiation or other environmental phenomena can cause DNA to break apart or rearrange its nucleotide base pairs in unhealthy ways. If such mutations are left unchecked, they can accumulate over time and lead, ultimately, to cancer or diabetes.

Elledge likened the DNA damage response to a command and control center: "It sends out sensors and sends out an alarm to start activating different repair pathways."

Elledge explained that two critical enzymes, known in scientific shorthand as ATM and ATR, act like sensors to detect trouble and initiate the DNA damage response by engaging the cell's molecular repair apparatus. By looking to see how ATM and ATR reacted to damage in cells, Elledge's group found that a small molecular army -- more than 700 different proteins -- is called into physiological actio

Contact: Jim Keeley
Howard Hughes Medical Institute

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