Recombination Mediator and Rad51 Targeting Activities of a Human BRCA2 Polypeptide

FILLIPO, Joseph, Peter CHI, Lumír KREJČÍ and Patrick SUNG. Recombination Mediator and Rad51 Targeting Activities of a Human BRCA2 Polypeptide. J. Biol. Chem. 2006, vol. 17, No 281, p. 11649-11657, 8 pp. ISSN 0021-9258.

Basic information

• Original name: Recombination Mediator and Rad51 Targeting Activities of a Human BRCA2 Polypeptide
• Name in Czech: Aktivity BRCA2 polypetidu jako rekombinačního mediátora
• Authors: FILLIPO, Joseph (840 United States of America), Peter CHI (840 United States of America), Lumír KREJČÍ (203 Czech Republic, guarantor) and Patrick SUNG (840 United States of America).
• Edition: J. Biol. Chem. 2006, 0021-9258.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 5.808
• RIV identification code: RIV/00216224:14310/06:00017411
• Organization unit: Faculty of Science
• UT WoS: 000236988100028
• Keywords in English: BRCA2-Rad51 interactions
• Tags: BRCA2-Rad51 interactions
• Tags: International impact, Reviewed

Abstract

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.

Abstract (in Czech)

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.

Links

• LC06030, research and development project: Name: Biomolekulární centrum

Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular centre

• ME 888, research and development project: Name: Srs2 protein a jeho multifunkční úloha při rekombinančních /opravných procesech

Investor: Ministry of Education, Youth and Sports of the CR, Srs2 protein and its multi-functional role in rekombination/repair processes

• MSM0021622413, plan (intention): Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment