Multiprotein Complex Repairs DNA Damage

Researchers working with a fruit fly model have identified a DNA repair complex that both marks the damaged site and facilitates its removal and repair.

Investigators at the Stowers Institute for Medical Research (Kansas City, MO, USA) showed that Tip60 (dTip60), a chromatin-remodeling complex in the fruit fly Drosophila melanogaster, acetylated the histone variant phospho-H2Av (damaged site) and exchanged it with an unmodified H2Av.

Results published in the December 17, 2004, issue of Science revealed that both the histone acetyltransferase dTip60 as well as the adenosine triphosphatase Domino/p400 catalyzed the exchange of phospho-H2Av. This finding marks the first report on a mechanism for selective histone exchange that uses the concerted action of two distinct chromatin-remodeling enzymes within the same multiprotein complex.

"DNA double strand breaks are regarded as one of the primary causes of cancer,” explained first author Dr. Thomas Kusch, senior research associate at the Stowers Institute for Medical Research. "While there are natural mechanisms within an organism to detect and repair these breaks, factors involved in DNA damage repair must first bypass histones. Histones are proteins that condense DNA and protect it from mechanical and other stresses, but also make DNA rather inaccessible.”



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Stowers Institute for Medical Research