Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer

Association of breast tumor susceptibility gene products BRCA1 and BRCA2 wi th the RAD51 recombination protein suggested that cancer could arise throug h defects in recombination, The identification of NBS1, responsible for Nij megen breakage syndrome, from the MRE11/RAD50 recombination protein complex also supports this hypothesis. However, our mutation analysis revealed tha t known members of the RAD52 epistasis group are rarely mutated in human pr imary 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 significantly 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 fi ndings suggest that RAD54B may play an active role in recombination process es 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 c hromosomal abnormalities. Homozygous mutations at highly conserved position s of RAD54B were observed in human primary lymphoma and colon cancer.