Functions of Human Rad51 and Other Recombination Factors in DNA Double-Strand Break Repair

Abstract

Abstract : Genes of the RAD52 epistasis group function in the repair of DNA double strand breaks. Genetic and biochemical studies have suggested that the function of the RAD52 group genes are highly conserved from yeast to humans and interestingly the efficiency of DNA double strand break repair in mammals is dependent on the tumor suppressors BRCAl and BRCA2. This underscores the importance of studying the mechanistic basis of the recombination machinery. The human Rad5 1 protein can catalyze homologous DNA pairing and strand exchange reaction. The reaction is stimulated by RPA but interestingly; RPA can also compete with Rad5 1 for binding sites on the DNA and therefore suppress the pairing and strand exchange activity of Rad5 1. Various proteins called recombination mediators are able to overcome the suppressive nature of the single strand binding proteins in prokaryotes and yeast cells. Interestingly five Rad5 1 like proteins, called Rad5 1 paralogs, have been identified in human cells. Here we show that two of those Rad5 1 paralogs, RadS 1 B and Rad5 1 C, are associated in a complex in human cells. Importantly, the complex is able to promote the Rad5 1 homologous pairing and strand exchange under conditions were Rad5 1 must compete with RPA for binding sites on the ssDNA template.