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 development of cancer. The cloning of human homologs of yeast DNA repair/cell cycle checkpoint genes should yield candidates for human tumor suppressor genes as well as identifying potential targets for cancer therapy. The Schizosaccharomyces pombe genes rad17, rad1, and hus1 have been identified as playing roles in DNA repair and cell cycle checkpoint control pathways. We have cloned the cDNA for the human homolog of S. pombe rad17, RAD17, which localizes 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. pombe 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, rad9, rad1, and hus1 from mouse, Caenorhabditis elegans, and Drosophila melanogaster. These include Rad17 and Rad9 from D. melanogaster, hpr-17 and hpr-1 from C. elegans, and RAD1 and HUS1 from mouse. The identification of homologs of the S. pombe rad checkpoint genes from mammals, arthropods, and nematodes indicates that this cell cycle checkpoint pathway is conserved throughout eukaryotes.
Dean
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The Rockefeller University, The Howard Hughes Medical Institute, 1230 York Avenue, New York, New York, 10021, USA. deanfb@mod.rockfeller.edu
Lian
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O'Donnell
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D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D051818:Replication Protein C; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; C501394:Rad17 protein, Drosophila; D029702:Schizosaccharomyces pombe Proteins; C106332:hus1 protein, S pombe; D004720:Endonucleases; C499354:rad1 protein, S pombe; D051818:Replication Protein C