The finding, reported in the Dec. 17, 2004, issue of the journal Cell, provides the first link between a cell's DNA repair machinery and its DNA storage and retrieval machinery. The two processes have been studied independently, and each is essential for proper care and maintenance of the cell's genetic material, but until now there was little evidence of how the two might work together.
"We have brought together two fields that are essential for proper maintenance of DNA," said Xuetong "Snow" Shen, assistant professor in the Department of Carcinogenesis at M. D. Anderson. "It was generally understood there must be a connection between the two, but no direct connection had ever been seen. We have bridged that gap."
Many types of cancer, including human leukemias and lymphomas, have been linked to defects in DNA maintenance. Shen's lab studied a particular protein complex, called INO80, that regulates access to DNA. Inside cells, long strands of DNA are wound tightly around a series of proteins called histones. The combination of DNA and its associated proteins is called chromatin. The histone proteins help compact the DNA and help keep it organized within the chromosome, said Shen, but DNA tightly wound around histones is inaccessible. If DNA becomes damaged by radiation, reactive chemicals or ultraviolet light, for example, it must be repaired. But the bulky repair proteins need to gain access to the damaged areas of DNA. That's where INO80 chromatin remodeling might comes in. Its role, discovered by Shen and his colleagues, is likely to loosen the damaged DNA from the grip of histone proteins so the DNA repair machinery can access the damaged section. When INO80 is not working properly, dama
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Contact: Julie A. Penne
jpenne@mdanderson.org
713-792-0655
University of Texas M. D. Anderson Cancer Center
16-Dec-2004