CHARACTERIZATION OF THE HUMAN HOMOLOG OF RAD54 - A GENE LOCATED ON CHROMOSOME 1P32 AT A REGION OF HIGH LOSS OF HETEROZYGOSITY IN BREAST-TUMORS

A search of the Human Genome Sciences database of expressed sequence-t agged DNA fragments, for sequences containing homology to known yeast DNA recombination and repair genes, yielded a cDNA fragment with high homology to RAD54. Here we describe the complete cDNA sequence and the characterization of the genomic locus coding for the human homologue of the yeast RAD54 gene (hRAD54). The yeast RAD54 belongs to the RAD52 epistasis group and appears to be involved in both DNA recombination and repair. The hRAD54 gene maps to chromosome 1p32 in a region of fre quent loss of heterozygosity in breast tumors and encodes a protein of M-r 93,000 that displays 52% identity to the yeast RAD54 protein. The hRAD54 protein sequence additionally contains all seven of the consen sus segments of a superfamily of proteins with presumed or proven DNA helicase activity. Mutations in genes with consensus helicase homology have been found in cancer-prone syndromes such as xeroderma pigmentos um and Bloom syndrome as well as Werner's syndrome, in which patients age prematurely, and the ii-linked mental retardation with alpha-thala ssemia syndrome, ATR-X. We have examined the hRAD54 gene in several br east tumors and breast tumor cell lines and, although the gene region appears to he deleted in several tumors, at present we have found no c oding sequence mutations.