cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein
cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein
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DOI：
10.1073/pnas.93.7.2850
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发表时间：
1996-04-02
影响因子：
11.1
通讯作者：
Schreiber, SL
中科院分区：
文献类型：
--
作者：
Cimprich, KA;Shin, TB;Schreiber, SL
最近鉴定了一个参与细胞周期进展、DNA 重组和 DNA 损伤检测的蛋白质家族，该家族的成员之一人类 ATM 在毛细血管扩张共济失调患者的细胞中存在缺陷，参与细胞对受损 DNA 的检测和反应，其他成员包括 Mei-41（黑腹果蝇）、Mec1p（酿酒酵母）和 Rad3（裂殖酵母） pombe），这是 S 和 G(2)/M 检查点所必需的，以及 FRAP（智人）和 Tor1/2p（酿酒酵母），它们参与导致 G(1) 细胞周期进展的雷帕霉素敏感途径。我们在这里报告了编码与该家族成员具有显着同源性的蛋白质的人类 cDNA 的克隆，从 Jurkat T 细胞 cDNA 文库分离的三个重叠克隆揭示了7.9-kb 开放阅读框编码我们命名为 FRP1（FRAP 相关蛋白）的蛋白质，具有 2644 个氨基酸，预测分子量为 301 kDa。利用荧光原位杂交和全长 cDNA FRP1 克隆，FRP1 基因已定位到染色体位点 3q22-q24。 FRP1 与参与检查点功能的三个 PIK 相关激酶家族成员（Mei-41、Mec1p 和 Rad3）关系最为密切，因此可能是这些蛋白质的功能性人类对应物。
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 G(2)/M checkpoints, as well as FRAP (Homo sapiens) and Tor1/2p (S. cerevisiae),which are involved in a rapamycin-sensitive pathway leading to G(1) 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.