Human and mouse homologs of the Schizosaccharomyces pombe rad17+ cell cycle checkpoint control gene

• Published in: Genomics (San Diego, Calif.) Vol. 55; no. 2; pp. 219 - 228
• Main Authors: BLUYSSEN, H. A. R, NAUS, N. C, VAN OS, R. I, JASPERS, I, HOEIJMAKERS, J. H. J, DE KLEIN, A
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 15.01.1999
• Subjects: Amino Acid Sequence; Animals; Arabidopsis Proteins; Base Sequence; Biological and medical sciences; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromosome Mapping; Chromosomes, Human, Pair 5; Chromosomes, Human, Pair 7; Conserved Sequence; DNA-Binding Proteins - genetics; Drosophila Proteins; Fundamental and applied biological sciences. Psychology; Genes. Genome; Homeodomain Proteins; Humans; Mice; Minor Histocompatibility Antigens; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nuclear Proteins; Phylogeny; Proto-Oncogene Proteins c-bcl-2; Pseudogenes; Replication Protein C; Repressor Proteins; RNA Splicing - genetics; RNA, Messenger - genetics; Saccharomyces cerevisiae Proteins; Schizosaccharomyces - genetics; Sequence Analysis, DNA; Sequence Homology; Tissue Distribution; Genetic mapping; Human; Nucleotide sequence; Rodentia; Tissue specificity; Homology; Chromosome B5; Gene expression; Testicle; Molecular evolution; Vertebrata; Mammalia; Shutdown; Complementary DNA; Mouse; Cell cycle
• DOI: 10.1006/geno.1998.5642
• ISSN: 0888-7543

The Schizosaccharomyces pombe rad17+ cell cycle checkpoint control gene is required for S-phase and G2/M arrest in response to both DNA damage and incomplete DNA replication. We isolated and characterized the putative human (RAD17Sp) and mouse (mRAD17Sp) homologs of the S. pombe Rad17 (Rad17Sp) protein. The human RAD17Sp open reading frame (ORF) encodes a protein of 681 amino acids; the mRAD17Sp ORF codes for a protein of 688 amino acids. The mRAD17Sp messenger is highly expressed in the testis as a single 3-kb mRNA species. The human RAD17Sp and mRAD17Sp proteins are 24% identical and 46% similar to the S.pombe Rad17Sp protein. Sequence homology was also noted with the Saccharomyces cerevisiae Rad24Sc (which is the structural counterpart of S.pombe Rad17Sp) and structurally related polypeptides from Caenorhabditis elegans, Arabidopsis thaliana, Pyrococcus horikoshii, and Drosophila melanogaster. The degree of conservation between the mammalian RAD17Sp proteins and those of the other species is consistent with the evolutionary distance between the species, indicating that these proteins are most likely true counterparts. In addition, homology was found between the Rad17Sp homologs and proteins identified as components of mammalian replication factor C (RF-C)/activator 1, especially in several highly conserved RF-C-like domains including a "Walker A" motif. Using FISH and analysis of a panel of rodent-human cell hybrids, the human RAD17Sp gene (HGMW-approved symbol RAD17 could be localized on human chromosome 5q13-q14, a region implicated in the etiology of small cell lung carcinoma, non-small-cell lung carcinoma, duodenal adenocarcinoma, and head and neck squamous cell carcinoma. Our results suggest that the structure and function of the checkpoint "rad" genes in the G2/M checkpoint pathway are evolutionary conserved between yeast and higher eukaryotes.