The Rad51 paralog Rad51B promotes homologous recombinational repair

The highly conserved Saccharomyces cerevisiae Rad51 protein plays a central role in both mitotic and meiotic homologous DNA recombination. Seven membe rs of the Rad51 family have been identified in vertebrate cells, including Rad51, Dmc1, and five Rad51-related proteins referred to as Rad51 paralogs, which share 20 to 30% sequence identity with Rad51. In chicken B lymphocyt e DT40 cells, we generated a mutant with RAD51B/RAD51L1, a member of the Ra d51 family, knocked out. RAD51B(-/-) cells are viable, although spontaneous chromosomal aberrations kill about 20% of the cells in each cell cycle. Ra d51B deficiency impairs homologous recombinational repair (HRR), as measure d by targeted integration, sister chromatid exchange, and intragenic recomb ination at the immunoglobulin locus. RAD51B(-/-) cells are quite sensitive to the cross-linking agents cisplatin and mitomycin C and mildly sensitive to gamma-rays. The formation of damage-induced Rad51 nuclear foci is much r educed in RAD51B(-/-) cells, suggesting that Rad51B promotes the assembly o f Rad51 nucleoprotein filaments during HRR. These findings show that Rad51B is important for repairing various types of DNA lesions and maintaining ch romosome integrity.