p53-dependent change in replication timing of the human genome |
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Authors: | Watanabe Yoshihisa Shibata Kiyoshi Sugimura Haruhiko Maekawa Masato |
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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 |
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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. |
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Keywords: | p53 Replication timing Cell-cycle checkpoint G1/S transition Human genome |
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