Recombination Mediator and Rad51 Targeting Activities of a Human BRCA2 Polypeptide

• Název česky: Aktivity BRCA2 polypetidu jako rekombinačního mediátora
• Autoři: FILLIPO Joseph; CHI Peter; KREJČÍ Lumír; SUNG Patrick
• Rok publikování: 2006
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: J. Biol. Chem.
• Fakulta / Pracoviště MU: Přírodovědecká fakulta
• 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.

Související projekty

• Proteiny v metabolismu a při interakci organismů s prostředím
• Biomolekulární centrum
• Srs2 protein a jeho multifunkční úloha při rekombinačních/opravných procesech