tailieunhanh - Báo cáo khoa học: BRCA1 16 years later: DNA damage-induced BRCA1 shuttling

he tumor suppressor, breast cancer susceptibility gene 1 (BRCA1), plays an integral role in the maintenance of genome stability and, in particular, the cellular response to DNA damage. Here, the emerging role of BRCA1 in nonhomologous end-joining-mediated DNA repair following DNA dam-age will be reviewed, as well as the activation of apoptotic pathways. | ỊFEBS Journal MINIREVIEW BRCA1 16 years later DNA damage-induced BRCA1 shuttling Eddy S. Yang1 and Fen Xia1 2 1 Department of Radiation Oncology Vanderbilt Ingram Cancer Center Vanderbilt University Schoolof Medicine Nashville TN USA 2 Department of Cancer Biology Vanderbilt Ingram Cancer Center Vanderbilt University Schoolof Medicine Nashville TN USA Keywords BRCA1 DNA damage DNA repair homologous recombination nonhomologous end-joining Correspondence F. Xia Department of Radiation Oncology Vanderbilt University Schoolof Medicine 2220 Pierce Ave B-1003 Preston Research Building Nashville TN 37232-5671 USA Fax 615 343 0161 Tel 615 322 2555 E-mail The tumor suppressor breast cancer susceptibility gene 1 BRCA1 plays an integral role in the maintenance of genome stability and in particular the cellular response to DNA damage. Here the emerging role of BRCA1 in nonhomologous end-joining-mediated DNA repair following DNA damage will be reviewed as well as the activation of apoptotic pathways. The control of these functions via DNA damage-induced BRCA1 shuttling will also be discussed in particular BRCA1 shuttling induced by erlotinib and irradiation. Finally the potential targeting of BRCA1 shuttling as a novel strategy to sensitize cells to DNA damage will be entertained. Received 25 January 2010 revised 15 April 2010 accepted 12 May 2010 doi Introduction Cells are constantly subjected to a variety of insults that endanger the integrity and fidelity of the genome. However several processes are in place to prevent or resolve the potential damage incurred including DNA damage response pathways to initiate cell cycle checkpoints execute repair of DNA damage and activate programmed cell death 1 . The breast cancer susceptibility gene 1 BRCA1 plays a central role in this manner. BRCA1 functions in a number of cellular processes including chromatin remodeling protein ubiquitina-tion DNA replication DNA repair regulation

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