DNA damage signal uncovered
3 June 2008
Damage to DNA is usually bad news, but when it happens in a cancer cell disarranged DNA can have a therapeutic up-side.
Understanding what causes DNA damage and the steps that lead to its repair in healthy cells can give insights into why cells become cancerous; this in turn suggests new ways to diagnose or treat cancer.
Now, scientists led by Professor Ashok Venkitaraman at the MRC Cancer Cell Unit in Cambridge have identified a signalling pathway that helps to initiate DNA repair. Knowing the steps that lead to restoration could make it possible to unravel repair or interrupt the pathway before the process begins.
Professor Venkitaraman explains:
‘‘Most current treatments for cancer work by inducing DNA damage. The new pathway this research has identified is triggered by a protein kinase called CK2, that signals when and where DNA is damaged, to help start its repair. We now need to find out if this pathway becomes active in cancer cells from patients undergoing treatment. If it does, in the future a drug designed to stop CK2 could help to boost the effect of other cancer therapies like radiation. Of course, CK2 performs many jobs in normal cells, so finding a selective way to stop it working in cancer cells will be a challenge.’’
The cell uses histones and other simple proteins bound to DNA as markers to sense when DNA has been damaged. The combination of DNA and proteins is known as chromatin, a material present in the nucleus of a cell. Professor Venkitaraman’s team have identified a change in chromatin that sparks the beginning of the DNA repair process.
Original research paper: HP1-ß mobilization promotes chromatin changes that initiate the DNA damage response, Ashok R. Venkitaraman et al is published in Nature.
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