Identification of a novel human Rad51 variant that promotes DNA strand exchange

Abstract

Rad51 plays a key role in the repair of DNA doublestrand breaks through homologous recombination, which is the central process in the maintenance of genomic integrity. Five paralogs of the human Rad51 gene (hRad51) have been identified to date, including hRad51B, hRad51C, hRad51D, Xrcc2 and Xrcc3. In searches of additional hRad51 paralogs, we identified a novel hRad51 variant that lacked the sequence corresponding to exon 9 (hRad51-Dex9). The expected amino acid sequence of hRad51-Dex9 showed a frame- shift at codon 259, which resulted in a truncated C-terminus. RT-PCR analysis revealed that both hRad51 and hRad51-Dex9 were prominently expressed in the testis, but that there were subtle differences in tissue specificity. The hRad51- Delta ex9 protein was detected as a 31-kDa protein in the testis and localized at the nucleus. In addition, the hRad51-Delta ex9 protein showed a DNA-strand exchange activity comparable to that of hRad51. Taken together, these results indicate that hRad51-Delta ex9 promotes homologous pairing and DNA strand exchange in the nucleus, suggesting that alternative pathways in hRad51- or hRad51-Delta ex9-dependent manners exist for DNA recombination and repair.