Association of breast tumor susceptibility gene products BRCA1 and BRCA2 with the RAD51 recombination protein suggested that cancer could arise through defects in recombination. The identi®cation of NBS1, responsible for Nijmegen breakage syndrome, from the MRE11/RAD50 recombination protein complex also supports this hypothesis. However, our mutation analysis revealed that known members of the RAD52 epistasis group are rarely mutated in human primary cancer. Here we describe the isolation of a novel member of the SNF2 superfamily, characterized with sequence motifs similar to those in DNA and RNA helicases. The gene, designated RAD54B, is signi®cantly homologous to the RAD54 recombination gene. The expression of RAD54B was high in testis and spleen, which are active in meiotic and mitotic recombination. These ®ndings suggest that RAD54B may play an active role in recombination processes in concert with other members of the RAD52 epistasis group. RAD54B maps to human chromosome 8q21.3-q22 in a region associated with cancer-related chromosomal abnormalities. Homozygous mutations at highly conserved positions of RAD54B were observed in human primary lymphoma and colon cancer. These ®ndings suggest that some cancers arise through alterations of the RAD54B function.

Members of the SNF2/SWI2 family, characterized with sequence motifs similar to those found in DNA and RNA helicases, play roles in various aspects of cellular fundamental processes such as transcriptional regulation, chromosome stability, nucleotide excision repair, and recombination. We have isolated a novel member of the human SNF2/SWI2 family, RAD54B, which is highly homologous to mammalian RAD54. The RAD54 gene is a member of the RAD52 epistasis group which is involved in the recombinational repair of DNA damage. Here we demonstrate that human Rad54B (hRad54B), like human Rad54 (hRad54), associates with human Rad51 (hRad51). Both hRad54B and hRad54 associate with hRad51 through their NH 2 -terminal domains, but there are differences in their ways of association with hRad51. In contrast to Rad54, whose association with Rad51 is induced by ionizing radiation, Rad54B associates with Rad51 constitutively in immunoprecipitation experiments. Also, the failure to detect the interaction between hRad54B and hRad51 in the yeast two-hybrid assay suggests that their interaction, unlike that between hRad54 and hRad51, may be indirect. Immunofluorescence microscopy revealed that hRad54B formed nuclear foci that colocalized with hRad51, hRad54, and BRCA1. These findings suggest that Rad54B may be functionally distinct from Rad54, although it may play an active role in recombination processes in concert with other members of the RAD52 epistasis group.The SNF2/SWI2 family is a still expanding superfamily of DNA-dependent ATPases. Members of this family are involved in various functions, such as transcriptional regulation (SNF2, MOT1, and BRM), chromosome stability (lodestar), nucleotide excision repair (ERCC6 and Rad16), and recombination (Rad54) (1). Recently, we cloned a novel gene of the SNF2/SWI2 family, RAD54B, which shares homology with mammalian and yeast RAD54 (2).In Saccharomyces cerevisiae, the RAD52 epistasis group genes are involved in the recombinational repair of DNA damage, including DNA double-strand breaks as well as playing a role in meiotic recombination (3), and it has been demonstrated that the RAD52 epistasis group genes are well conserved structurally and functionally throughout evolution (4). RAD54 is a member of the RAD52 epistasis group. Yeast Rad54 stimulates homologous DNA pairing by Rad51 (5), and it was shown that homozygous RAD54 mutants in mouse and chicken are highly radiation-and methyl methanesulfonate-sensitive and have reduced levels of homologous recombination (6, 7).Human RAD54B encodes a protein of 910 amino acids. The central part, which contains the seven helicase motifs found in members of the SNF2/SWI2 family, is well conserved between hRad54 and hRad54B, whereas the NH 2 -terminal region is less conserved except the first 10 amino acids (2). The expression pattern of RAD54B coincides with those of members of the RAD52 epistasis group, although the functions of Rad54B are unknown. It has been shown that in mammals, as well as in yeast, the proteins of the RAD52 epistasis group inte...