Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes

Megumi Toyoshima, Tsutomu Shimura, Satish Kumar Adiga, Masataka Taga, Kazunori Shiraishi, Masao Inoue, Zhi Min Yuan, Ohtsura Niwa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cell cycle arrest in response to DNA damage is important for the maintenance of genomic integrity in higher eukaryotes. We have previously reported the novel p53-dependent S-phase checkpoint operating in mouse zygotes fertilized with irradiated sperm. In the present study, we analysed the detail of the p53 function required for this S-phase checkpoint in mouse zygotes. The results indicate that ATM kinase is likely to be indispensable for the p53-dependent S-phase checkpoint since the suppression was abrogated by inhibitors such as caffeine and wortmannin. However, ATM phosphorylation site mutant proteins were still capable of suppressing DNA synthesis when microinjected into sperm-irradiated zygotes lacking the functional p53, suggesting that the target of the phosphorylation is not p53. In addition, the suppression was not affected by α-amanitin, and p53 protein mutated at the transcriptional activation domain was also functional in the suppression of DNA synthesis. However, p53 proteins mutated at the DNA-binding domain were devoid of the suppressing activity. Taken together, the transcription-independent function of p53 associated with the DNA-binding domain is involved in the S-phase checkpoint in collaboration with yet another unidentified target protein(s).

Original languageEnglish
Pages (from-to)3229-3235
Number of pages7
JournalOncogene
Volume24
Issue number20
DOIs
Publication statusPublished - 05-05-2005

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S Phase Cell Cycle Checkpoints
Zygote
Spermatozoa
DNA
Phosphorylation
Amanitins
Proteins
Mutant Proteins
Cell Cycle Checkpoints
Caffeine
Eukaryota
Transcriptional Activation
DNA Damage
Phosphotransferases
Maintenance

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Toyoshima, M., Shimura, T., Adiga, S. K., Taga, M., Shiraishi, K., Inoue, M., ... Niwa, O. (2005). Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes. Oncogene, 24(20), 3229-3235. https://doi.org/10.1038/sj.onc.1208514
Toyoshima, Megumi ; Shimura, Tsutomu ; Adiga, Satish Kumar ; Taga, Masataka ; Shiraishi, Kazunori ; Inoue, Masao ; Yuan, Zhi Min ; Niwa, Ohtsura. / Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes. In: Oncogene. 2005 ; Vol. 24, No. 20. pp. 3229-3235.
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abstract = "Cell cycle arrest in response to DNA damage is important for the maintenance of genomic integrity in higher eukaryotes. We have previously reported the novel p53-dependent S-phase checkpoint operating in mouse zygotes fertilized with irradiated sperm. In the present study, we analysed the detail of the p53 function required for this S-phase checkpoint in mouse zygotes. The results indicate that ATM kinase is likely to be indispensable for the p53-dependent S-phase checkpoint since the suppression was abrogated by inhibitors such as caffeine and wortmannin. However, ATM phosphorylation site mutant proteins were still capable of suppressing DNA synthesis when microinjected into sperm-irradiated zygotes lacking the functional p53, suggesting that the target of the phosphorylation is not p53. In addition, the suppression was not affected by α-amanitin, and p53 protein mutated at the transcriptional activation domain was also functional in the suppression of DNA synthesis. However, p53 proteins mutated at the DNA-binding domain were devoid of the suppressing activity. Taken together, the transcription-independent function of p53 associated with the DNA-binding domain is involved in the S-phase checkpoint in collaboration with yet another unidentified target protein(s).",
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Toyoshima, M, Shimura, T, Adiga, SK, Taga, M, Shiraishi, K, Inoue, M, Yuan, ZM & Niwa, O 2005, 'Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes', Oncogene, vol. 24, no. 20, pp. 3229-3235. https://doi.org/10.1038/sj.onc.1208514

Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes. / Toyoshima, Megumi; Shimura, Tsutomu; Adiga, Satish Kumar; Taga, Masataka; Shiraishi, Kazunori; Inoue, Masao; Yuan, Zhi Min; Niwa, Ohtsura.

In: Oncogene, Vol. 24, No. 20, 05.05.2005, p. 3229-3235.

Research output: Contribution to journalArticle

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T1 - Transcription-independent suppression of DNA synthesis by p53 in sperm-irradiated mouse zygotes

AU - Toyoshima, Megumi

AU - Shimura, Tsutomu

AU - Adiga, Satish Kumar

AU - Taga, Masataka

AU - Shiraishi, Kazunori

AU - Inoue, Masao

AU - Yuan, Zhi Min

AU - Niwa, Ohtsura

PY - 2005/5/5

Y1 - 2005/5/5

N2 - Cell cycle arrest in response to DNA damage is important for the maintenance of genomic integrity in higher eukaryotes. We have previously reported the novel p53-dependent S-phase checkpoint operating in mouse zygotes fertilized with irradiated sperm. In the present study, we analysed the detail of the p53 function required for this S-phase checkpoint in mouse zygotes. The results indicate that ATM kinase is likely to be indispensable for the p53-dependent S-phase checkpoint since the suppression was abrogated by inhibitors such as caffeine and wortmannin. However, ATM phosphorylation site mutant proteins were still capable of suppressing DNA synthesis when microinjected into sperm-irradiated zygotes lacking the functional p53, suggesting that the target of the phosphorylation is not p53. In addition, the suppression was not affected by α-amanitin, and p53 protein mutated at the transcriptional activation domain was also functional in the suppression of DNA synthesis. However, p53 proteins mutated at the DNA-binding domain were devoid of the suppressing activity. Taken together, the transcription-independent function of p53 associated with the DNA-binding domain is involved in the S-phase checkpoint in collaboration with yet another unidentified target protein(s).

AB - Cell cycle arrest in response to DNA damage is important for the maintenance of genomic integrity in higher eukaryotes. We have previously reported the novel p53-dependent S-phase checkpoint operating in mouse zygotes fertilized with irradiated sperm. In the present study, we analysed the detail of the p53 function required for this S-phase checkpoint in mouse zygotes. The results indicate that ATM kinase is likely to be indispensable for the p53-dependent S-phase checkpoint since the suppression was abrogated by inhibitors such as caffeine and wortmannin. However, ATM phosphorylation site mutant proteins were still capable of suppressing DNA synthesis when microinjected into sperm-irradiated zygotes lacking the functional p53, suggesting that the target of the phosphorylation is not p53. In addition, the suppression was not affected by α-amanitin, and p53 protein mutated at the transcriptional activation domain was also functional in the suppression of DNA synthesis. However, p53 proteins mutated at the DNA-binding domain were devoid of the suppressing activity. Taken together, the transcription-independent function of p53 associated with the DNA-binding domain is involved in the S-phase checkpoint in collaboration with yet another unidentified target protein(s).

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