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p53-dependent change in replication timing of the human genome
Authors:Watanabe Yoshihisa  Shibata Kiyoshi  Sugimura Haruhiko  Maekawa Masato
Institution:a Department of Laboratory Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan
b Equipment Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan
c Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan
Abstract:The tumor suppressor gene p53 has roles in multiple cell-cycle checkpoints, including the G1/S transition, to prevent replication of cells with DNA damage. p53 is thought to be associated with regulation of replication timing during S-phase in the human genome. In the present study, we used p53-wild-type and p53-null HCT116 colon carcinoma cells to analyze p53-dependent changes in replication timing of the human genome. The percentage of HCT116 p53(−/−) cells in S-phase was higher than that of HCT116 p53(+/+) cells. We compared replication timing of human genes between the two cell lines using 25,000 human cDNA microarray. We identified genes that replicated earlier in HCT116 p53(−/−) cells than in HCT116 p53(+/+) cells. These genes included cell-cycle- and apoptosis-related genes. We propose that p53 plays a role in regulation of replication timing of the human genome through the control of cell-cycle checkpoints.
Keywords:p53  Replication timing  Cell-cycle checkpoint  G1/S transition  Human genome
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