Recombination Mediator and Rad51 Targeting Activities of a Human BRCA2 Polypeptide
| Název česky | Aktivity BRCA2 polypetidu jako rekombinačního mediátora |
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| Autoři | |
| Rok publikování | 2006 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | J. Biol. Chem. |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | http://www.jbc.org/cgi/content/abstract/281/17/11649 |
| Obor | Biochemie |
| Klíčová slova | BRCA2-Rad51 interactions |
| Popis | BRCA2 likely exerts its tumor suppressor function by enhancing the efficiency of the homology-directed repair of injured chromosomes. To help define the DNA repair role of BRCA2, we expressed and purified a polypeptide, BRC3/4-DBD, that harbors its BRC3 and BRC4 repeats and DNA binding domain. BRC3/4-DBD interacted with hRad51 and bound DNA with a distinct preference for single-stranded (ss) DNA. Importantly we demonstrated by biochemical means and electron microscopy that BRC3/4-DBD nucleates hRad51 onto ssDNA and acts as a recombination mediator in enabling hRad51 to utilize replication protein A-coated ssDNA as recombination substrate. These functions of BRC3/4-DBD required both the BRC repeats and the BRCA2 DNA binding domain. The results thus clarify the role of BRCA2 in Rad51-dependent DNA recombination and repair, and the experimental strategies described herein should be valuable for systematically deciphering this BRCA2 function. |
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