hXRCC2 Enhances ADP/ATP Processing and Strand Exchange by hRAD51*
- Genetics and Molecular Biology Program, Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
- ↵‡ To whom correspondence should be addressed: Kimmel Cancer Center–BLSB933, 233 S. 10th St., Philadelphia, PA 19107. Tel.: 215-503-1345; Fax: 215-503-6739; E-mail: rfishel{at}lac.jci.tju.edu.
Abstract
The assembly of bacterial RecA, and its human homolog hRAD51, into an operational ADP/ATP-regulated DNA-protein (nucleoprotein) filament is essential for homologous recombination repair (HRR). Yet hRAD51 lacks the coordinated ADP/ATP processing exhibited by RecA and is less efficient in HRR reactions in vitro. In this study, we demonstrate that hXRCC2, one of five other poorly understood non-redundant human mitotic RecA homologs (hRAD51B, hRAD51C, hRAD51D, hXRCC2, and hXRCC3), stimulates hRAD51 ATP processing. hXRCC2 also increases hRAD51-mediated DNA unwinding and strand exchange activities that are integral for HRR. Although there does not seem to be a long-lived interaction between hXRCC2 and hRAD51, we detail a strong adenosine nucleotide-regulated interaction between the hXRCC2-hRAD51D heterodimer and hRAD51. These observations begin to elucidate the separate and specialized functions of the human mitotic RecA homologs that enable an efficient nucleoprotein filament required for HRR.
- Received June 9, 2003.
- Revision received April 29, 2004.
- The American Society for Biochemistry and Molecular Biology, Inc.
