Investigadores de Penn Llegan al Home en Posible Gen de CáncerContributed by: AdminStaff1 · Views: 971
Contributed by: AdminStaff1 · May 25, 2007 @ 06:51 AM MDT · Views: 971
Penn Researchers Home In On Possible New Breast Cancer Gene
PHILADELPHIA) – Researchers at the Abramson Family Cancer Research Institute of the University of Pennsylvania and the Dana-Farber Cancer Institute describe in this week’s issue of Science a new candidate breast-cancer susceptibility gene. The Rap80 gene is required for the normal DNA-repair function of the well-known breast cancer gene BRCA1.
BRCA1 and Rap80 are recruited to the same structures at DNA damage sites in human cells treated with ionizing radiation.
In this study, the researchers found Rap80 binds to the region of the BRCA1 protein that is necessary for recognizing sites of DNA damage. In the 1990s, investigators discovered that BRCA1 was involved in DNA repair by maintaining the normal number and structure of chromosomes. DNA breaks that aren't repaired can lead to cancer by increasing the rate of mutations, cancer-causing changes in the gene sequence.
More specifically, modification of proteins in the cell nucleus – by another protein called ubiquitin – that are tightly bound to DNA are responsible for signaling BRCA1 via Rap80 to action. Rap80 binds to specific types of ubiquitin that concentrate at DNA damage sites, enabling BRCA1 to be recruited to sites of damage.
BRCA1 and BRCA2 mutations account for less than 50 percent of inherited breast cancer. “The genetic basis of breast cancers in other families has been largely unknown,” explains Greenberg. “These families aren’t able to make informed choices about screening and treatment, prophylactic or otherwise, the way the BRCA families can.”
Researchers from multiple labs, including Penn and those led by co-senior author David M. Livingston at Dana-Farber, are finding that many of these non-BRCA families have mutations in genes that have a relationship with BRCA1. Many of the genes that encode these proteins are also altered in familial breast cancer.
Depletion of Rap80 from human cells (right panel) reduces the ability of BRCA1 to migrate to laser-induced DNA damage sites as compared to control cells (left panel).
This research was funded by the National Cancer Institute and startup funds from the Abramson Family Cancer Research Institute.
Co-authors are Bijan Sobhian, David M. Livingston, Aedín C. Culhane, Lisa Moreau, and Bing, Xia from Dana Farber, and Genze Shao and Dana R. Lilly from Penn.
Courtesy of Penn Medicine