Identification of a human homologue of the Schizosaccharomyces pombe rad17+ checkpoint gene.
In the fission yeast Schizosaccharomyces pombe the rad17+ gene is required for both the DNA damage-dependent and the DNA replication-dependent cell cycle checkpoints. We have identified a human cDNA homologue of the S. pombe rad17+ checkpoint gene, designated Hrad17. Hrad17 has 49% identity to the S. pombe rad17+ sequence at the DNA level and 49% identity and 72% similarity at the amino acid level. Northern blot analysis indicates elevated levels of expression in testis and in cancer cell lines. Chromosomal localization by fluorescence in situ hybridization indicates that Hrad17 is located on chromosome 4q13.3-21.2. This region is subject to loss of heterozygosity in several human cancers. To begin to understand the protein-protein interactions of the human checkpoint machinery, we have used the yeast two-hybrid system to examine potential interactions between Hrad1, Hrad9, and Hrad17. We demonstrate a physical interaction between Hrad17 and Hrad1 but no interaction with Hrad9.
Parker
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AE
Department of Experimental Molecular Biology, Janssen Research Foundation, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Van de Weyer
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I
Laus
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MC
Verhasselt
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P
Luyten
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WH
D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002871:Chromosome Banding; D002894:Chromosomes, Human, Pair 4; D004249:DNA Damage; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D018816:Genes, cdc; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C113575:Rad17 protein, human; D029702:Schizosaccharomyces pombe Proteins; C501114:rad24 protein, S pombe; D005090:Exodeoxyribonucleases; D005092:Exonucleases; C113574:Rad1 protein, human; D043211:Exodeoxyribonuclease V