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BRCA2's Role in Homologous Recombination Through Interaction with RAD51
Author(s) -
D'Ausilio Morgan,
Beckman Andrew,
Brown Grace,
Emeghara Udochi,
Ho Felicia,
Malzberg Ethan,
Spellman Brandon,
Tavan Ketaki,
Xiao Jeffrey,
Jensen Ryan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb261
Subject(s) - rad51 , homologous recombination , dna , sister chromatids , dna repair , genome instability , protein filament , brca2 protein , biology , recombinase , dna damage , microbiology and biotechnology , genetics , mutation , recombination , gene , germline mutation , chromosome
BRCA2 serves as a key mediator in error‐free DNA repair through homologous recombination (HR). Damaged DNA is repaired using identical portions of DNA from the sister chromatid which serves as a template for HR. BRCA2 binds RAD51, a recombinase capable of forming a nucleoprotein filament with single stranded DNA (ssDNA). BRCA2 then guides RAD51 to the site of DNA damage to catalyze the process of HR. BRCA2 has eight BRC repeats, which are highly conserved regions that bind multiple RAD51 molecules to promote nucleoprotein filament formation. The structure of BRCA2 BRC4‐RAD51 revealed that the BRC repeats are able to mimic the interaction of the RAD51‐RAD51 filament interface, providing a scaffold to nucleate filament growth. The Pingry School SMART Team, in conjunction with MSOE Center for BioMolecular Modeling, used 3‐D modeling and printing technology to further examine the structure‐function relationship of BRCA2 and RAD51. If BRCA2 is unable to bind RAD51 due to mutations, the resulting genomic instability can contribute to tumorigenesis. The Pingry School SMART Team aims to utilize the BRCA2‐RAD51 and the RAD51‐ssDNA filament structural models to investigate the roles of these proteins in HR and their link to breast and ovarian cancer.