DNA Repair Promoted by Rec 2

Weill Medical College Of Cornell Univ, New York NY

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Abstract

DESCRIPTION (provided by applicant): Two RecA homologs have been identified in Ustilago mavids. One is orthologous to Rad5 I while the other is a structurally divergent protein encoded by the REC2 gene. Both are necessary for proficiency in the repair of DNA damage, meiotic and mitotic recombination, and maintenance of the genetic Integrity of the organism. Biochemical evidence indicates that Rec2 performs the catalytic function of homologous pairing and DNA strand exchange more effectively than Rad51 These findings challenge the current dogma established in studies using yeast and human systems that feature Rad5 1 as the central catalytic component of a double-strand-break-repair complex. In this proposal we seek to understand the relationship between Rec2 and Rad51 We also plan to investigate the relationship of Rec2 and Rad 51 with Brh2 a newly discovered homolog of BRCA2, the product of a human breast cancer gene. The BRH2 gene was identified in a mutant screen for DNA repair deficiency. Three aims are proposed. First, we will study interaction between Rec2 and Rad5 1 in promoting several homologous pairing and strand transfer reactions. Second, we will investigate the BRH2 gene and examine its genetic and biochemical interactions with REC2 and RAD5I. Third. We have discovered a novel mode of plasmid replication in U. mavdis that appears to depend upon REC2 gene function and posttranscriptional gene silencing, and plan several experiments to establish these relationships in a definitive manner. We believe that the studies proposed here will provide novel insight into the basis of homologous pairing processes and provide new insight into the function of a gene important in human breast cancer.