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CSHL-led team identifies key decision-point at which cells with broken DNA repair themselves or die
Date:4/10/2009

When cells undergo potentially catastrophic damage, for example as a result of exposure to ionizing radiation, they must make a decision: either to fix the damage or program themselves for death, a process called apoptosis.

It's a stark decision that is as mysterious as it is remarkable, involving what might be described metaphorically as a network of internal alarms that detect damage to DNA packed tightly in the cell nucleus. In intricate ways, cells orchestrate a response to signals from such resident sensors when they are triggered by exposure to radiation or other toxic processes, which if unchecked can cause genes to mutate and cancerous tumors to begin forming.

A team of biologists led by Professor Nicholas Tonks, Ph.D., F.R.S., of Cold Spring Harbor Laboratory (CSHL), this week revealed results of experiments suggesting at least one way in which cascades of intracellular signals are regulated at what they call a decision point as cells decide whether to repair broken DNA strands or commit suicide following DNA damage.

In a report published online ahead of print in the Journal of Biological Chemistry, Tonks and colleagues identify a protein with the unlikely name Eyes Absent, or EYA, as performing a critical role in setting the damage-repair machinery in motion. Engaged within the larger context of a complex signaling cascade within the cell, EYA regulates the formation of specialized microenvironments on DNA, called gamma-H2A.X foci, which allow the cell to summon repair enzymes to the site of broken DNA strands. The team's experiments, conducted by Navasona Krishnan, Ph.D., of the Tonks lab, showed that when Eyes Absent was not present in damaged cells grown in culture, such foci were not formed and the cells went the route of apoptosisthey programmed themselves to die.

'A lovely moment' of discovery

Tonks says the finding is "a powerful example of multiple lines of research and differen
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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