cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein.

Cimprich, K A; Shin, T B; Keith, C T; Schreiber, S L

doi:10.1073/pnas.93.7.2850

Cited by 273DNA Repair MechanismsPI3K/AKT/mTOR signaling in cancerCancer-related Molecular Pathways

cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein.

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Cimprich, K A, Shin, T B, Keith, C T, Schreiber, S L·1996·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.93.7.2850PMC PMC39722

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Abstract

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.

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ATR is essential for early embryonic development.
“ATR was originally cloned as a member of the phosphoinositide 3-kinase–related kinase (PIKK) family and is essential for early embryonic development [32, 80, 81].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [80]

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Authors: Cimprich, K. A., Shin, T. B., Keith, C. T., & Schreiber, S. L.
Affiliations: Howard Hughes Medical Institute (US)
ORCID: Cimprich, K A
Schreiber, S L
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1996-04-02
Volume: 93
Issue: 7
Pages: 2850-2855
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.93.7.2850
PMC: PMC39722
OpenAlex: W2034306661
Cited by: 273
References: 43
Citations by year: 2026: 3 · 2025: 2 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 7 · 2018: 6 · 2017: 14 · 2016: 3 · 2015: 7 · 2014: 5 · 2013: 8 · 2012: 4
FWCI: 8.84
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (GM38627)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords: cell cycle checkpoints, DNA damage response, G1 cell cycle progression, ataxia telangiectasia, mei-41, Rad3, gene mapping, cDNA cloning
MeSH terms: Amino Acid Sequence, Animals, Ataxia Telangiectasia, Base Sequence, Cell Cycle, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 3, Cloning, Molecular, DNA Damage, Drosophila melanogaster, Female, Fungal Proteins, Humans, Karyotyping, Male, Molecular Sequence Data, Organ Specificity, Phylogeny, Pregnancy, Protein Kinases, Recombination, Genetic, Saccharomyces cerevisiae, Schizosaccharomyces, T-Lymphocytes, Restriction Mapping, Gene Library, Conserved Sequence, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, In Situ Hybridization, Fluorescence, DNA Primers, DNA, Complementary, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins

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cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein.

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