PUBLIC RELEASE DATE:

19-Dec-2013

Contact: Scott LaFee slafee@ucsd.edu 619-543-6163 University of California - San Diego

Researchers at the University of California, San Diego School of Medicine, with colleagues in The Netherlands and United Kingdom, have produced the first map detailing the network of genetic interactions underlying the cellular response to ultraviolet (UV) radiation.

The researchers say their study establishes a new method and resource for exploring in greater detail how cells are damaged by UV radiation and how they repair themselves. UV damage is one route to malignancy, especially in skin cancer, and understanding the underlying repair pathways will better help scientists to understand what goes wrong in such cancers.

The findings will be published in the December 26, 2013 issue of Cell Reports.

Principal investigator Trey Ideker, PhD, division chief of genetics in the UC San Diego School of Medicine and a professor in the UC San Diego Departments of Medicine and Bioengineering, and colleagues mapped 89 UV-induced functional interactions among 62 protein complexes. The interactions were culled from a larger measurement of more than 45,000 double mutants, the deletion of two separate genes, before and after different doses of UV radiation.

Specifically, they identified interactive links to the cell's chromatin structure remodeling (RSC) complex, a grouping of protein subunits that remodel chromatin the combination of DNA and proteins that make up a cell's nucleus during cell mitosis or division. "We show that RSC is recruited to places on genes or DNA sequences where UV damage has occurred and that it helps facilitate efficient repair by promoting nucleosome remodeling," said Ideker.

The process of repairing DNA damage caused by UV radiation and other sources, such as chemicals and other mutagens, is both simple and complicated. DNA-distorting lesions are detected by a cellular mechanism called the nucleotide excision repair (NER) pathway. The lesion is excised; the gap filled with new genetic material copied from an intact DNA strand by special enzymes; and the remaining nick sealed by another specialized enzyme.

However, NER does not work in isolation; rather it coordinates with other biological mechanisms, including RSC.

Visit link:
How cells remodel after UV radiation

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