Mammalian Gene Plays Key Role In Genome Integrity And Tumor Suppression

NEW YORK (Reuters Health) - Findings from a new animal study suggest that the Mus81 gene plays an important role in ensuring genomic integrity. Moreover, say researchers, if the human version functions like its murine counterpart, then it could represent a critical tumor suppressor gene.

Previous reports have implicated Mus81, a DNA endonuclease, in the rescue of stalled replication forks, according to the report published in the June 18th issue of Science.

In the new study, Dr. Razqallah Hakem, from the University of Toronto, and colleagues used gene targeting to evaluate the physiologic requirements of Mus81 in mice.

Animals completing lacking Mus81 were still viable and fertile, suggesting that the enzyme is not essential for meiosis-related processes. Although Mus81 deficiency increased sensitivity to mitomycin C-mediated DNA damage, it did not affect sensitivity to gamma-radiation.

Evidence of a possible role as a tumor suppressor gene came when the authors compared the effects of hetero- and homozygous Mus81 deficiency. Both states produced a dramatic and equivalent increase in the susceptibility to spontaneous chromosome damage, lymphomas, and other cancers.

“These studies demonstrate a critical role for the proper biallelic expression of the mammalian Mus81 in the maintenance of genomic integrity and tumor suppression,” the researchers conclude.

Source: Science 2004;304:1822-1826. [ Google search on this article ]

MeSH Headings:Neoplasms: Genes, p53: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.

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