Interactions Among Brac1, Brac2, and Components of the Recombination Machinery

摘要

DNA double-strand breaks are induced by endogenous free radicals and environmental agents such as ionizing radiation. The repair of DNA double-strand breaks is important for preventing possible chromosomal fragmentation, translocations, and deletions induced by these breaks. The accurate repair of DNA double-strand breaks is mediated by a group of genes called the RAD52 epistasis group and proceeds via a recombinational mechanism. In mammals, the efficiency of recombinational DNA repair is modulated by the tumor suppressors BRCA1 and BRCA2, providing compelling evidence that this DNA repair pathway functions to suppress cancer formation. Importantly, recombinational DNA repair is also required for the removal of interstrand DNA crosslinks formed by bifunctional crosslinking agents, which are commonly used to treat various malignancies. Our research efforts arc directed at establishing biochemical models for examining the functions of the various RAD52 group components and for delineating the mechanism of recombinational DNA repair. Recent studies in our laboratory have established an in vitro system for examining the recombinase activity of human Rad51 and have demonstrated that human Rad51B and Rad51C proteins are associated as a stable complex. Together with our collaborators, BRCA2 protein has been expressed in insect cells with the use of a recombinant baculovirus. Ongoing studies address the functional and physical interactions among the aforementioned and other recombination factors of the RAD52 group.