DNA Repair Proteins Monitored At Double-Strand Break

Investigators at St.
Jude Children's Research Hospital had a molecule's eye view of the human
cell's DNA repair kit as it assembled on a double-strand break to link
together the broken ends. Double-strand breaks are ruptures that cut
completely across the twisted, ladder-like structure of DNA, breaking it
into two pieces.



The St. Jude researchers could determine when repair proteins arrived
at or around the DNA break and evaluate its repair -- even when particular
proteins shifted away from the break to make room for others. A report on
this work appears in the May 7 online issue of "Nature Cell Biology."



The findings are important because disruption of the precise movement
of these repair proteins can cause mutations, cell death or cancer, and the
ability to track the process so closely will give researchers critical
insights into what can go wrong with DNA repair. This could lead to novel
ways to make cancer cells more sensitive to therapy by blocking their
ability to repair double-stranded breaks caused by chemotherapy or
radiation. It could also suggest new strategies for enhancing repair of
double-stranded DNA caused by radiation, natural oxidants in food or the
body, and other toxins that can cause disease and aging.



"Prior to this work, there was no practical and efficient way to find
and study the DNA repair proteins that organize themselves on and around a
double- strand break in human cells," said Michael Kastan, M.D., Ph.D., St.
Jude Cancer Center director. "Our approach solved that problem and allowed
us to document the cell's response to double-strand DNA breaks over time."
Kastan is the paper's senior author.



The assay, developed by Elijahu Berkovich, Ph.D., in Kastan's
laboratory, demonstrates how key repair proteins, such as ATM, NBS1, XRCC4
and gamma-H2AX, interact to coordinate repair of double-strand breaks.



The other author of this article was Raymond Monnat, M.D. (University
of Washington).



This work was supported in part by the National Institutes of Health
and ALSAC.



St. Jude Children's Research Hospital



St. Jude Children's Research Hospital is internationally recognized for
its pioneering work in finding cures and saving children with cancer and
other catastrophic diseases. Founded by late entertainer Danny Thomas and
based in Memphis, Tenn., St. Jude freely shares its discoveries with
scientific and medical communities around the world. No family ever pays
for treatments not covered by insurance, and families without insurance are
never asked to pay. St. Jude is financially supported by ALSAC, its
fundraising organization. For more information, please visit
stjude.


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