cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein.
A family of proteins involved in cell cycle progression, DNA recombination, and the detection of DNA damage has been recently identified. One of the members of this family, human ATM, is defective in the cells of patients with ataxia telangiectasia and is involved in detection and response of cells to damaged DNA. Other members include Mei-41 (Drosophila melanogaster), Mec1p (Saccharomyces cerevisiae), and Rad3 (Schizosaccharomyces pombe), which are required for the S and G2/M checkpoints, as well as FRAP (Homo sapiens) and Torl/2p (S. cerevisiae), which are involved in a rapamycin-sensitive pathway leading to G1 cell cycle progression. We report here the cloning of a human cDNA encoding a protein with significant homology to members of this family. Three overlapping clones isolated from a Jurkat T-cell cDNA library revealed a 7.9-kb open reading frame encoding a protein that we have named FRP1 (FRAP-related protein) with 2644 amino acids and a predicted molecular mass of 301 kDa. Using fluorescence in situ hybridization and a full-length cDNA FRP1 clone, the FRP1 gene has been mapped to the chromosomal locus 3q22-q24. FRP1 is most closely related to three of the PIK-related kinase family members involved in checkpoint function--Mei-41, Mec1p, and Rad3--and as such may be the functional human counterpart of these proteins.
Cimprich
K A
KA
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Shin
T B
TB
Keith
C T
CT
Schreiber
S L
SL
D000595:Amino Acid Sequence; D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004249:DNA Damage; D017931:DNA Primers; D018076:DNA, Complementary; D004331:Drosophila melanogaster / Q000235:genetics; D005260:Female; D005656:Fungal Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D015723:Gene Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D011247:Pregnancy; D011494:Protein Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes
D018797:Cell Cycle Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D005656:Fungal Proteins; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases