CDNA cloning and Gene Mapping of Human Homologs for Schizosaccharomyces pombe rad17, rad1, and hus1 and cloning of homologs from mouse, Caenorhabditis elegans, and Drosophila melanogaster

Mutations in DNA repair/cell cycle checkpoint genes can lead to the develop ment of cancer. The cloning of human homologs of yeast DNA repair/cell cycl e checkpoint genes should yield candidates for human tumor suppressor genes as well as identifying potential targets for cancer therapy. The Schizosac charomyces pombe genes rad17, rad1, and hus1 have been identified as playin g roles in DNA repair and cell cycle checkpoint control pathways. We have c loned the cDNA for the human homolog of S. pombe rad17, RAD17, which locali zes to chromosomal location 5q13 by fluorescence in situ hybridization and radiation hybrid mapping; the cDNA for the human homolog of S. pombe rad1, RAD1, which maps to 5p14-p13.2; and the cDNA for the human homolog of S. po mbe hus1, HUS1, which maps to 7p13-p12. The human gene loci have previously been identified as regions containing tumor suppressor genes. In addition, we report the cloning of the cDNAs for genes related to S. pombe rad17, ra d9, rad1, and hus1 from mouse, Caenorhabditis elegans, and Drosophila melan ogaster. These include Rad17 and Rad9 from D. melanogaster, hpr-17 and hpr- l from C. elegans, and RAD1 and HUS1 from mouse. The identification of homo logs of the S. pombe rad checkpoint genes from mammals, arthropods, and nem atodes indicates that this cell cycle checkpoint pathway is conserved throu ghout eukaryotes. (C) 1998 Academic Press.