cDNA Cloning and Gene Mapping of a Candidate Human Cell Cycle Checkpoint Protein

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 7; pp. 2850 - 2855
• Main Authors: Cimprich, Karlene A., Shin, Tae Bum, Keith, Curtis T., Schreiber, Stuart L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 02.04.1996; National Acad Sciences; National Academy of Sciences
• Subjects: Amino Acid Sequence; Animals; Ataxia Telangiectasia - genetics; Ataxia Telangiectasia Mutated Proteins; Base Sequence; Cell cycle; Cell Cycle - genetics; Cell Cycle Proteins - biosynthesis; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Line; Cellular biology; Chromosome Mapping; Chromosomes, Human, Pair 3; Cloning, Molecular; Complementary DNA; Conserved Sequence; Deoxyribonucleic acid; DNA; DNA Damage; DNA Primers; DNA, Complementary; Drosophila melanogaster - genetics; Female; Fungal Proteins - biosynthesis; Fungal Proteins - chemistry; Fungal Proteins - genetics; Gene Library; Genes; Genetic loci; Genetics; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Male; Mathematical functions; Molecular Sequence Data; Open reading frames; Organ Specificity; Phylogeny; Pregnancy; Protein Kinases - biosynthesis; Protein Kinases - chemistry; Protein Kinases - genetics; Protein-Serine-Threonine Kinases; Proteins; Recombination, Genetic; Restriction Mapping; Saccharomyces cerevisiae - genetics; Schizosaccharomyces - genetics; Sequence Homology, Amino Acid; T lymphocytes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.7.2850

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 Tor1/2p (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.