Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation

Yuzuru Minemoto, Sanae Uchida, Motoaki Ohtsubo, Mari Shimura, Toshiyuki Sasagawa, Masato Hirata, Hitoshi Nakagama, Yukihito Ishizaka, Katsumi Yamashita

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10 Citations (Scopus)

Abstract

Most cell lines that lack functional p53 protein are arrested in the G2 phase of the cell cycle due to DNA damage. When the G2 checkpoint is abrogated, these cells are forced into mitotic catastrophe. A549 lung adenocarcinoma cells, in which p53 was eliminated with the HPV16 E6 gene, exhibited efficient arrest in the G2 phase when treated with adriamycin. Administration of caffeine to G2-arrested cells induced a drastic change in cell phenotype, the nature of which depended on the status of p53. Flow cytometric and microscopic observations revealed that cells that either contained or lacked p53 resumed their cell cycles and entered mitosis upon caffeine treatment. However, transit to the M phase was slower in p53-negative cells than in p53-positive cells. Consistent with these observations, CDK1 activity was maintained at high levels, along with stable cyclin B1, in p53-negative cells. The addition of butyrolactone I, which is an inhibitor of CDK1 and CDK2, to the p53-negative cells reduced the floating round cell population and induced the disappearance of cyclin B1. These results suggest a relationship between the p53 pathway and the ubiquitin-mediated degradation of mitotic cyclins and possible cross-talk between the G2-DNA damage checkpoint and the mitotic checkpoint.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume412
Issue number1
DOIs
Publication statusPublished - Apr 1 2003

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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    Minemoto, Y., Uchida, S., Ohtsubo, M., Shimura, M., Sasagawa, T., Hirata, M., Nakagama, H., Ishizaka, Y., & Yamashita, K. (2003). Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation. Archives of Biochemistry and Biophysics, 412(1), 13-19. https://doi.org/10.1016/S0003-9861(03)00010-9