p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2

Mark W. Jackson, Mukesh K. Agarwal, Jinbo Yang, Patrick Bruss, Takeshi Uchiumi, Munna L. Agarwal, George R. Stark, William R. Taylor

Research output: Contribution to journalReview article

73 Citations (Scopus)

Abstract

The progression of normal cells from G2 into mitosis is stably blocked when their DNA is damaged. Tumor cells lacking p53 arrest only transiently in G2, but eventually enter mitosis. We show that an important component of the stable G2 arrest in normal cells is the transcriptional repression of more than 20 genes encoding proteins needed to enter into and progress through mitosis. Studies from a number of labs including our own have shown that, by inducing p53 and p21/WAF1, DNA damage can trigger RB-family-dependent transcriptional repression. Our studies reported here show that p130 and p107 play a key role in transcriptional repression of genes required for G2 and M in response to DNA damage. For plk1, repression is partially abrogated by loss of p130 and p107, and is completely abrogated by loss of all three RB-family proteins. Mouse cells lacking RB-family proteins do not accumulate with a 4N content of DNA when exposed to adriamycin, suggesting that all three RB-family proteins contribute to G2 arrest in response to DNA damage. Stable arrest in the presence of functional p53-to-RB signaling is probably due to the ability of cells to exit the cell cycle from G2, a conclusion supported by our observation that KI67, a marker of cell-cycle entry, is downregulated in both G1 and G2 in a p53-dependent manner.

Original languageEnglish
Pages (from-to)1821-1832
Number of pages12
JournalJournal of Cell Science
Volume118
Issue number9
DOIs
Publication statusPublished - May 1 2005

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DNA Damage
Cell Cycle
Mitosis
Proteins
DNA
Doxorubicin
Down-Regulation
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Jackson, M. W., Agarwal, M. K., Yang, J., Bruss, P., Uchiumi, T., Agarwal, M. L., ... Taylor, W. R. (2005). p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2. Journal of Cell Science, 118(9), 1821-1832. https://doi.org/10.1242/jcs.02307

p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2. / Jackson, Mark W.; Agarwal, Mukesh K.; Yang, Jinbo; Bruss, Patrick; Uchiumi, Takeshi; Agarwal, Munna L.; Stark, George R.; Taylor, William R.

In: Journal of Cell Science, Vol. 118, No. 9, 01.05.2005, p. 1821-1832.

Research output: Contribution to journalReview article

Jackson, MW, Agarwal, MK, Yang, J, Bruss, P, Uchiumi, T, Agarwal, ML, Stark, GR & Taylor, WR 2005, 'p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2', Journal of Cell Science, vol. 118, no. 9, pp. 1821-1832. https://doi.org/10.1242/jcs.02307
Jackson, Mark W. ; Agarwal, Mukesh K. ; Yang, Jinbo ; Bruss, Patrick ; Uchiumi, Takeshi ; Agarwal, Munna L. ; Stark, George R. ; Taylor, William R. / p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2. In: Journal of Cell Science. 2005 ; Vol. 118, No. 9. pp. 1821-1832.
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