XRCC3 is required for efficient repair of chromosome breaks by homologous recombination

XRCC3 was originally identified as a human gene able to complement the DNA damage sensitivity, chromosomal instability and impaired growth of the muta nt hamster cell line irs1SF. More recently, it has been cloned, sequenced a nd found to bear sequence homology to the highly conserved eukaryotic repai r and recombination gene RAD51. The phenotype of irs1SF and the identificat ion of XRCC3 as a member of the RAD51 gene family have suggested a role for XRCC3 in repair of DNA damage by homologous recombination. Homologous reco mbinational repair (HRR) of a specifically induced chromosomal double-stran d break (DSB) was assayed in irs1SF cells with and without transient comple mentation by human XRCC3;I. Complementation with XRCC3 increased the freque ncies of repair by 34- to 260-fold. The results confirm a role for XRCC3 in HRR of DNA DSB, and the importance of this repair pathway for the maintena nce of chromosomal integrity in mammalian cells. (C) 2000 Elsevier Science B.V. All rights reserved.