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Permanent cell cycle exit in G2 phase after DNA damage in normal human fibroblasts
Open accessAbstract
Although the Cdk inhibitor p21(Waf1/Cip1), one of the transcriptional targets of p53, has been implicated in the maintenance of G(2) arrest after DNA damage, its function at this stage of the cell cycle is not really understood. Here, we show that the exposure of normal human fibroblasts (NHFs) to genotoxic agents provokes permanent cell cycle exit in G(2) phase, whereas mouse embryo fibroblasts and transformed human cells progress through mitosis and arrest in G(1) without intervening cytokinesis. p21(Waf1/Cip1) exerts a key role in driving this G(2) exit both by inhibiting cyclin B1-Cdk1 and cyclin A-Cdk1/2 complexes, which control G(2)/M progression, and by blocking the phosphorylation of pRb family proteins. NHFs with compromised pRb proteins could still efficiently arrest in G(2) but were unable to exit the cell cycle, resulting in cell death. Our experiments show that, when under continuous genotoxic stress, normal cells can reverse their commitment to mitotic progression due to passage through the restriction point and that mechanisms involving p21(Waf1/Cip1) and pocket proteins can induce exit in G(2) and G(1).
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In the citing paper
“In fact, cyclin B1–CDK1 complexes bound to p21 in the nucleus are inactive and cannot be activated upon CDK1 dephosphorylation by phosphatase CDC25C [60,61].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [60]
In the citing paper
“In primary fibroblasts exposed to genotoxic drugs, in addition to inhibiting cyclin A-Cdk1/2 complexes, 59 p21 also associates with and sequesters inactive cyclin B1-Cdk1 complexes in the nucleus, thereby preventing mitotic entry 69 (Fig. 2).”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [59]
In the citing paper
“Based on these findings, it was proposed that the “G2 exit program” might serve as a safeguard mechanism to prevent cell adaptation to the G2 checkpoint and consequently the passage into mitosis of cells with damaged DNA (Fig. 2; 59 ).”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [59]
In the citing paper
“Prolonged exposure to this drug led to p53/p21dependent irreversible cell cycle exit in G2 that was associated with down-regulation of both cyclin A and cyclin B1 and accumulation of non-phosphorylated pRb family pocket proteins.59”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [59]
In the citing paper
“In the absence of sustained Chk1/2 activation, p53/p21-deficient cells exposed to genotoxic agents arrest only transiently in G2 and then progress into mitosis and eventually die.59,93”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [59]
In the citing paper
“In the absence of sustained Chk1/2 activation, p53/p21-deficient cells exposed to genotoxic agents arrest only transiently in G2 and then progress into mitosis and eventually die.59,93”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [59]
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Cites
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
CDK inhibitors: positive and negative regulators of G1-phase progression
Sherr, C. J., & Roberts, J. M. (1999) · Genes & Development · doi:10.1101/gad.13.12.1501 · Cited by 6,115
p53 is required for radiation-induced apoptosis in mouse thymocytes
Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., & Jacks, T. (1993) · Nature · doi:10.1038/362847a0 · Cited by 2,864
Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53
Scheffner, M., Huibregtse, J. M., Vierstra, R. D., & Howley, P. M. (1993) · Cell · doi:10.1016/0092-8674(93)90384-3 · Cited by 2,416
Cell cycle checkpoint signaling through the ATM and ATR kinases
Abraham, R. T. (2001) · Genes & Development · doi:10.1101/gad.914401 · Cited by 1,966
Regulation of the G2/M transition by p53
Taylor, W. R., & Stark, G. R. (2001) · Oncogene · doi:10.1038/sj.onc.1204252 · Cited by 1,584
Dulić, V., Kaufmann, W. K., Wilson, S. J., Tisty, T. D., Lees, E., Harper, J. W., Elledge, S. J., & Reed, S. I. (1994) · Cell · doi:10.1016/0092-8674(94)90379-4 · Cited by 1,465
Self-citationCyclin A is required at two points in the human cell cycle.
Pagano, M., Pepperkok, R., Verde, F., Ansorge, W. J., & Draetta, G. F. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05135.x · Cited by 1,403
Peng, C.-Y., Graves, P. R., Thoma, R. S., Wu, Z., Shaw, A. S., & Piwnica-Worms, H. (1997) · Science · doi:10.1126/science.277.5331.1501 · Cited by 1,341
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Dittmann, C., Doueiri, S., Kluge, R., Dommisch, H., Gaber, T., & Pischon, N. (2015) · Journal of Periodontology · doi:10.1902/jop.2015.150032 · Cited by 15
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Bujňáková, Z. L., Kello, M., Kováč, J., Tóthová, E., Shpotyuk, O. I., Baláž, P., Mojžíš, J., & Andrejko, S. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2020.110683 · Cited by 12
Takeuchi, R., Matsumoto, H., Akimoto, Y., & Fujii, A. (2011) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2011.03.006 · Cited by 12
Takeuchi, R., Hiratsuka, K., Arikawa, K., Ono, M., Komiya, M., Akimoto, Y., Fujii, A., & Matsumoto, H. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13410 · Cited by 12
Pizarro, J. G., Folch, J., de la Torre, A. V., Junyent, F., Verdaguer, E., Jordán, J., Pallàs, M., & Camins, A. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22528 · Cited by 12
Tomas, F., Roux, P., & Gire, V. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07213-4 · Cited by 11
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Hu, Y.-C., Hsieh, B.-S., Cheng, H.-L., Huang, L., Huang, T.-C., Huang, I., & Chang, K. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.01.008 · Cited by 11
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Kollárovič, G., Studencka‐Turski, M., Ivanova, L., Lauenstein, C., Heinze, K., Lapytsko, A., Talemi, S. R., Figueiredo, A. S., & Schaber, J. (2016) · Aging · doi:10.18632/aging.100883 · Cited by 11
Acute exposure of human lung cells to 1,3-butadiene diepoxide results in G1 and G2 cell cycle arrest
Schmiederer, M., Knutson, E. P., Muganda, P. M., & Albrecht, T. (2005) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20099 · Cited by 10
Xue, J., Zhou, G., Chen, T., Gao, S., Choi, M.-H., & Wong, Y. (2013) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24680 · Cited by 9
Possible involvement of DNA breaks in epigenetic regulation of cell differentiation
Sjakste, N., & Sjakste, T. (2007) · Russian Journal of Genetics · doi:10.1134/s1022795407050018 · Cited by 9
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Schwarz, L. V., Valera, M. J., Delamare, A. P. L., Carrau, F., & Echeverrigaray, S. (2022) · Current Research in Microbial Sciences · doi:10.1016/j.crmicr.2022.100129 · Cited by 6
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Hossain, M. S., Kurokawa, K., & Sekimizu, K. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2004.09.033 · Cited by 6
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Lockwood, N., Martini, S., Lopez-Pardo, A., Deiss, K., Segeren, H. A., Semple, R. K., Collins, I., Repana, D., Cobbaut, M., Soliman, T. N., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-21-1785 · Cited by 5
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Woo, L. A., Wintruba, K. L., Wissmann, B., Tkachenko, S., Kubicka, E., Farber, E., Engkvist, O., Barrett, I. P., Granberg, K. L., Plowright, A. T., et al. (2024) · iScience · doi:10.1016/j.isci.2024.110485 · Cited by 4
Nam, D., Park, J., Lee, J., Son, J., & Kim, J. (2024) · Cellular Signalling · doi:10.1016/j.cellsig.2024.111402 · Cited by 3
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de Boer, H. R., Llobet, S. G., & van Vugt, M. A. T. M. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2279-x · Cited by 3
Segeren, H. A., van Rijnberk, L. M., Moreno, E., Riemers, F., van Liere, E. V., Yuan, R.-X., Wubbolts, R., de Bruin, A., & Westendorp, B. (2020) · bioRxiv · doi:10.1101/2020.03.19.998674 · Cited by 32
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González-Rajal, Á., McCloy, R. A., Nobis, M., Marzec, K. A., Chin, V. T., Hastings, J. F., Lai, K., Kennerson, M. L., Vaghjiani, V., Hughes, W. E., et al. (2021) · Research Explorer (The University of Manchester) · doi:10.1101/2020.11.26.400499
Johmura, Y., & Nakanishi, M. (2016) · Springer eBooks · doi:10.1007/978-4-431-55873-6_18
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Lossaint, G., Horvat, A., Gire, V., Bačević, K., Mrouj, K., Charrier‐Savournin, F., Georget, V., Fisher, D., & Dulić, V. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.17.452482
Self-citationMuto, J., Fukuda, S., Watanabe, K., Dai, X., Tsuda, T., Kiyoi, T., Mori, H., Shiraishi, K., Murakami, M., Higashiyama, S., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.06.463325
Philipot, D. (2012) · theses.fr (ABES) · doi:10.70675/9b4773fdz718bz4ff2za6ebz25081c8e24f5
Bačević, K. (2016) · theses.fr (ABES) · doi:10.70675/11789f75zbd23z4799zacfbzd7a0d55a3fd3
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Eriksson, D., Riklund, K., Johansson, L. F., & Stigbrand, T. I. (2008) · Springer eBooks · doi:10.1007/978-1-4020-8696-0_14
Metadata
- Authors
- Baus, F., Gire, V., Fisher, D., Piette, J., & Dulić, V.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Dulić, Vjekoslav
- Venue
- The EMBO Journal
- Published
- 2003-08-01
- Volume
- 22
- Issue
- 15
- Pages
- 3992-4002
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC169060
- OpenAlex
- W2035568149
- Cited by
- 143
- References
- 39
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 10 · 2019: 3 · 2018: 7 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 6 · 2013: 11 · 2012: 9
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Israel Cancer Research Fund
- Ligue Contre le Cancer
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- G2 phase, DNA damage, p21, p53, normal human fibroblasts, CDK1-cyclin B1, retinoblastoma protein phosphorylation, restriction point, genotoxic stress, cell death, G2/M transition, mitotic progression
- MeSH terms
- Bleomycin, Cells, Cultured, DNA Damage, Fibroblasts, Humans, Mitosis, Piperazines, G2 Phase, Cyclins, Cyclin-Dependent Kinases, Cyclin-Dependent Kinase Inhibitor p21, Diketopiperazines
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