Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

RAD54B: A novel RAD54 homologue that interacts with BRCA1 and RAD51

K Miyagawa MD, K Tanaka MD

Dept Molecular Pathology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan,

AIMS: BRCA1 and BRCA2 are mutated in a small fraction of breast cancer. Since they form a protein complex with recombination proteins including RAD51 and RAD54, it is possible that other proteins associated with BRCA are involved in tumor development. Therefore, we isolated a novel RAD54 homologue RAD54B and characterized its function. METHODS: To find a gene homologous to RAD54, an EST fragment was used to screen a human testis library. We examined protein-protein interaction by immunoprecipitation and immunofluorescence microscopy. A panel of 45 primary tumors including lymphomas and colorectal cancers was screened for RAD54B mutation. RESULTS: RAD54B encodes a protein of 910 amino acids highly homologous to yeast and human RAD54 at the C-terminal half region containing putative ATPase motifs. High levels of expression were observed in testis and spleen. RAD54B associates with RAD51 and forms nuclear foci that colocalize with RAD51, RAD54 and BRCA1. RAD54B maps to human chromosome 8q21.3 in a region associated with cancer-related chromosome abnormalities. Homozygous mutations at highly conserved positions were found in a small fraction of cancer. CONCLUSIONS: RAD54B forms a protein complex with RAD51, RAD54 and BRCA1. RAD54B may play an active role in recombination processes. Some cancers arise through alterations of the RAD54B function.

KEY WORDS: DNA repair.

For more information, contact

Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic instability.