Mitotic UV Irradiation Induces a DNA Replication-Licensing Defect that Potentiates G1 Arrest Response
Open accessAbstract
Cdt1 begins to accumulate in M phase and has a key role in establishing replication licensing at the end of mitosis or in early G1 phase. Treatments that damage the DNA of cells, such as UV irradiation, induce Cdt1 degradation through PCNA-dependent CRL4-Cdt2 ubiquitin ligase. How Cdt1 degradation is linked to cell cycle progression, however, remains unclear. In G1 phase, when licensing is established, UV irradiation leads to Cdt1 degradation, but has little effect on the licensing state. In M phase, however, UV irradiation does not induce Cdt1 degradation. When mitotic UV-irradiated cells were released into G1 phase, Cdt1 was degraded before licensing was established. Thus, these cells exhibited both defective licensing and G1 cell cycle arrest. The frequency of G1 arrest increased in cells expressing extra copies of Cdt2, and thus in cells in which Cdt1 degradation was enhanced, whereas the frequency of G1 arrest was reduced in cell expressing an extra copy of Cdt1. The G1 arrest response of cells irradiated in mitosis was important for cell survival by preventing the induction of apoptosis. Based on these observations, we propose that mammalian cells have a DNA replication-licensing checkpoint response to DNA damage induced during mitosis.
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As a consequence, the license is blocked after the cell enters G1 phase, and G1 arrest occurs.
“As a consequence the “license” is blocked after the cell enters into the G1 phase of cell cycle (G1 arrest occurs) [76].”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [76]
Morino et al. observed CDT1 degradation in M phase upon UV irradiation.
“Morino et al. observed CDT1 degradation in M phase upon UV irradiation.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [76]
CDT1 seems to be involved in formation of the pre-replication complex by replication licensing in late M phase or early G1 phase.
“Another regulatory protein—DNA replication factor Cdt1 (CDT1)—seems to be involved in the formation of the pre-replication complex by replication “licensing” in the late M phase or early G1 phase.”
From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [76]
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1 retracted
Mitosis Inhibits DNA Double-Strand Break Repair to Guard Against Telomere Fusions
Orthwein, A., Fradet‐Turcotte, A., Noordermeer, S. M., Canny, M. D., Brun, C. M., Strecker, J. G., Escribano‐Diaz, C., & Durocher, D. (2014) · Science · doi:10.1126/science.1248024 · Cited by 319 · see citing works
RetractedThe DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368 · see citing works
DNA Replication in Eukaryotic Cells
Bell, S. P., & Dutta, A. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135425 · Cited by 2,065 · see citing works
The DNA Damage Response: Ten Years After
Harper, J. W., & Elledge, S. J. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.11.015 · Cited by 1,705 · see citing works
Preventing re-replication of chromosomal DNA
Blow, J. J., & Dutta, A. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1663 · Cited by 664 · see citing works
Molecular Mechanisms of Mammalian Global Genome Nucleotide Excision Repair
Gillet, L. C. J., & Schärer, O. D. (2006) · Chemical Reviews · doi:10.1021/cr040483f · Cited by 642 · cited 1× · see citing works
“Nucleotide excision repair (NER) is a versatile system for repairing UV-induced DNA lesions [21,22,23,24].”
BackgroundJin, J., Arias, E. E., Chen, J., Harper, J. W., & Walter, J. C. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.08.010 · Cited by 632 · see citing works
Ordering S phase and M phase in the cell cycle
Nurse, P. (1994) · Cell · doi:10.1016/0092-8674(94)90539-8 · Cited by 595 · see citing works
Eukaryotic Chromosome DNA Replication: Where, When, and How?
Masai, H., Matsumoto, S., You, Z., Yoshizawa-Sugata, N., & Oda, M. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.052308.103205 · Cited by 494 · see citing works
The Cdt1 protein is required to license DNA for replication in fission yeast
Nishitani, H., Lygerou, Z., Nishimoto, T., & Nurse, P. (2000) · Nature · doi:10.1038/35007110 · Cited by 469 · see citing works
Self-citationThe fission yeast cdc18+ gene product couples S phase to START and mitosis
Kelly, T. J., Martin, G. S., Forsburg, S. L., Stephen, R. J., Russo, A. A., & Nurse, P. (1993) · Cell · doi:10.1016/0092-8674(93)90427-r · Cited by 442 · see citing works
A multistep damage recognition mechanism for global genomic nucleotide excision repair
Sugasawa, K., Okamoto, T., Shimizu, Y., Masutani, C., Iwai, S., & Hanaoka, F. (2001) · Genes & Development · doi:10.1101/gad.866301 · Cited by 435 · see citing works
Higa, L. A., Wu, M., Ye, T., Kobayashi, R., Sun, H., & Zhang, H. (2006) · Nature Cell Biology · doi:10.1038/ncb1490 · Cited by 414 · see citing works
Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cellsPreprint
Arias, E. E., & Walter, J. C. (2007) · Genes & Development · doi:10.1101/gad.1508907 · Cited by 405 · see citing works
Piatti, S., Lengauer, C., & Nasmyth, K. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00048.x · Cited by 397 · see citing works
Two E3 ubiquitin ligases, SCF‐Skp2 and DDB1‐Cul4, target human Cdt1 for proteolysis
Nishitani, H., Sugimoto, N., Roukos, V., Nakanishi, Y., Saijo, M., Obuse, C., Tsurimoto, T., Nakayama, K., Nakayama, K., Fujita, M., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601002 · Cited by 392 · see citing works
Self-citationMarti, T. M., Hefner, E., Feeney, L., Natale, V., & Cleaver, J. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603779103 · Cited by 359 · see citing works
Araújo, S. J., Tirode, F., Coin, F., Pospiech, H., Syväoja, J. E., Stucki, M., Hübscher, U., Egly, J., & Wood, R. D. (2000) · Genes & Development · doi:10.1101/gad.14.3.349 · Cited by 334 · see citing works
DNA damage signaling in response to double-strand breaks during mitosis
Giunta, S., Belotserkovskaya, R., & Jackson, S. P. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200911156 · Cited by 321 · see citing works
PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication
Arias, E. E., & Walter, J. C. (2005) · Nature Cell Biology · doi:10.1038/ncb1346 · Cited by 314 · see citing works
Nishitani, H., Taraviras, S. L., Lygerou, Z., & Nishimoto, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105406200 · Cited by 254 · see citing works
Self-citationControl of DNA replication licensing in a cell cycle
Nishitani, H., & Lygerou, Z. (2002) · Genes to Cells · doi:10.1046/j.1365-2443.2002.00544.x · Cited by 251 · see citing works
Self-citationPCNA Is a Cofactor for Cdt1 Degradation by CUL4/DDB1-mediated N-terminal Ubiquitination
Senga, T., Sivaprasad, U., Zhu, W., Park, J. H., Arias, E. E., Walter, J. C., & Dutta, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512705200 · Cited by 250 · see citing works
Nishitani, H., Shiomi, Y., Iida, H., Michishita, M., Takami, T., & Tsurimoto, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806045200 · Cited by 241 · see citing works
Self-citationMechanism of CRL4Cdt2, a PCNA-dependent E3 ubiquitin ligasePreprint
Havens, C. G., & Walter, J. C. (2011) · Genes & Development · doi:10.1101/gad.2068611 · Cited by 223 · see citing works
DNA repair: From molecular mechanism to human disease
Friedberg, E. C., Aguilera, A., Gellert, M. F., Hanawalt, P. C., Hays, J. B., Lehmann, A. R., Lindahl, T. L., Lowndes, N. F., Sarasin, A. R., & Wood, R. D. (2006) · DNA repair · doi:10.1016/j.dnarep.2006.05.005 · Cited by 193 · see citing works
Havens, C. G., & Walter, J. C. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.05.012 · Cited by 178 · see citing works
Cell type-specific responses of human cells to inhibition of replication licensing
Shreeram, S., Sparks, A., Lane, D. P., & Blow, J. J. (2002) · Oncogene · doi:10.1038/sj.onc.1205910 · Cited by 173 · see citing works
DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpointPreprint
Sansam, C. L., Shepard, J. L., Lai, K., Ianari, A., Danielian, P. S., Amsterdam, A., Hopkins, N. H., & Lees, J. A. (2006) · Genes & Development · doi:10.1101/gad.1482106 · Cited by 170 · see citing works
Abbas, T., & Dutta, A. (2011) · Cell Cycle · doi:10.4161/cc.10.2.14530 · Cited by 144 · see citing works
Implication of p53 in base excision DNA repair: in vivo evidence
Seo, Y. R., Fishel, M. L., Amundson, S. A., Kelley, M. R., & Smith, M. L. (2002) · Oncogene · doi:10.1038/sj.onc.1205129 · Cited by 115 · see citing works
DNA nucleotide excision repair-dependent signaling to checkpoint activation
Marini, F., Nardo, T., Giannattasio, M., Minuzzo, M., Stefanini, M., Plevani, P., & Falconi, M. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605446103 · Cited by 114 · see citing works
Raman, M., Havens, C. G., Walter, J. C., & Harper, J. W. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.036 · Cited by 108 · see citing works
DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1
Ralph, E., Boye, E., & Kearsey, S. E. (2006) · EMBO Reports · doi:10.1038/sj.embor.7400827 · Cited by 91 · see citing works
Peterson, S., Li, Y., Chait, B. T., Gottesman, M. E., Baer, R. J., & Gautier, J. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201103103 · Cited by 83 · see citing works
Origin licensing and p53 status regulate Cdk2 activity during G1
Nevis, K. R., Cordeiro‐Stone, M., & Cook, J. G. (2009) · Cell Cycle · doi:10.4161/cc.8.12.8811 · Cited by 73 · see citing works
Replication licensing promotes cyclin D1 expression and G1progression in untransformed human cells
Liu, P., Slater, D., Lenburg, M. E., Nevis, K. R., Cook, J. G., & Vaziri, C. (2009) · Cell Cycle · doi:10.4161/cc.8.1.7528 · Cited by 57 · see citing works
Chandrasekaran, S., Tan, T. X., Hall, J. R., & Cook, J. G. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.06163-11 · Cited by 46 · see citing works
Havens, C. G., Shobnam, N., Guarino, E., Centore, R. C., Zou, L., Kearsey, S. E., & Walter, J. C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.337683 · Cited by 45 · see citing works
Miotto, B., & Struhl, K. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.021 · Cited by 45 · see citing works
Dynamic recruitment of licensing factor Cdt1 to sites of DNA damage
Roukos, V., Kinkhabwala, A., Colombelli, J., Kotsantis, P., Taraviras, S. L., Nishitani, H., Stelzer, E. H. K., Bastiaens, P. I. H., & Lygerou, Z. (2011) · Journal of Cell Science · doi:10.1242/jcs.074229 · Cited by 40 · see citing works
Self-citationMichishita, M., Morimoto, A., Ishii, T., Komori, H., Shiomi, Y., Higuchi, Y., & Nishitani, H. (2010) · Genes to Cells · doi:10.1111/j.1365-2443.2010.01464.x · Cited by 38 · see citing works
Self-citationIshii, T., Shiomi, Y., Takami, T., Murakami, Y., Ohnishi, N., & Nishitani, H. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.161661 · Cited by 35 · see citing works
Self-citationCdt1 Is Differentially Targeted for Degradation by Anticancer Chemotherapeutic Drugs
Σταθοπούλου, Α., Roukos, V., Petropoulou, C., Kotsantis, P., Karantzelis, N., Nishitani, H., Lygerou, Z., & Taraviras, S. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034621 · Cited by 30 · see citing works
Self-citationJascur, T. A., Fotedar, R., Greene, S., Hotchkiss, E. C., & Boland, C. R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.221341 · Cited by 23 · see citing works
Shiomi, Y., Hayashi, A., Ishii, T., Shinmyozu, K., Nakayama, J., Sugasawa, K., & Nishitani, H. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06506-11 · Cited by 23 · see citing works
Self-citationLau, E. K., Chiang, G. G., Abraham, R. T., & Jiang, W. B. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e09-01-0022 · Cited by 20 · see citing works
Preventing DNA Re-Replication: Divergent Safeguards in Yeast and Metazoa
Feng, H., & Kipreos, E. T. (2003) · Cell Cycle · doi:10.4161/cc.2.5.527 · Cited by 16 · see citing works
Sakaguchi, H., Takami, T., Yasutani, Y., Maeda, T., Morino, M., Ishii, T., Shiomi, Y., & Nishitani, H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046480 · Cited by 13 · see citing works
Self-citationImaging Analysis to Determine Chromatin Binding of the Licensing Factor MCM2-7 in Mammalian Cells
Morino, M., Tanaka, M., Shiomi, Y., & Nishitani, H. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-0888-2_29 · Cited by 4 · see citing works
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- [10]Abbas T, Dutta A (2011) CRL4Cdt2: master coordinator of cell cycle progression and genome stability. Cell Cycle 10: 241– 249. 21212733 PMC3025761
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Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies
Kciuk, M., Marciniak, B., Mojzych, M., & Kontek, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197264 · Cited by 168 · see citing works
“As a consequence the “license” is blocked after the cell enters into the G1 phase of cell cycle (G1 arrest occurs) [76].”
BackgroundUSP37 deubiquitinates Cdt1 and contributes to regulate DNA replication
Hernández-Pérez, S., Cabrera, E., Amoedo, H., Rodríguez‐Acebes, S., Koundrioukoff, S., Debatisse, M., Méndez, J., & Freire, R. (2016) · Molecular Oncology · doi:10.1016/j.molonc.2016.05.008 · Cited by 41 · see citing works
Tanaka, M., Takahara, M., Nukina, K., Hayashi, A., Sakai, W., Sugasawa, K., Shiomi, Y., & Nishitani, H. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1295179 · Cited by 15 · see citing works
Self-citationCRL4Cdt2 Ubiquitin Ligase, A Genome Caretaker Controlled by Cdt2 Binding to PCNA and DNA
Mazian, M. A., Yamanishi, K., Rahman, M. Z. A., Ganasen, M., & Nishitani, H. (2022) · Genes · doi:10.3390/genes13020266 · Cited by 14 · see citing works
Self-citationDNA damage mediated by UV radiation and relative repair mechanisms in mammals
Wang, Y., Deng, X., & Zhou, M. (2022) · Genome Instability & Disease · doi:10.1007/s42764-022-00090-1 · Cited by 13 · see citing works
Nukina, K., Hayashi, A., Shiomi, Y., Sugasawa, K., Ohtsubo, M., & Nishitani, H. (2018) · Genes to Cells · doi:10.1111/gtc.12563 · Cited by 11 · see citing works
Self-citationShiomi, Y., Hayashi, A., Saito, Y., Kanemaki, M. T., & Nishitani, H. (2025) · Genes to Cells · doi:10.1111/gtc.70006 · Cited by 1 · see citing works
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- Authors
- Morino, M., Nukina, K., Sakaguchi, H., Maeda, T., Takahara, M., Shiomi, Y., & Nishitani, H.
- Affiliations
- University of Hyogo (JP)
- Corresponding author
- Nishitani, Hideo
- ORCID
- Nishitani, Hideo
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-03-23
- Volume
- 10
- Issue
- 3
- Pages
- e0120553
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4370595
- OpenAlex
- W1965221920
- Cited by
- 7
- References
- 50
- Citations by year
- 2025: 1 · 2022: 2 · 2020: 1 · 2018: 1 · 2017: 1 · 2016: 1
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (25430171, 26291025)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- Cdt1, Cdt2, DNA replication licensing, G1 cell cycle arrest, PCNA, DNA damage checkpoint, apoptosis inhibition, cell cycle progression
- MeSH terms
- Chromatin, DNA Damage, DNA Replication, Gene Expression Regulation, Humans, Mitosis, Nuclear Proteins, Ultraviolet Rays, Cell Cycle Proteins, Ubiquitin-Protein Ligases, Cell Line, Tumor, Protein Stability, G1 Phase Cell Cycle Checkpoints, Proteolysis, Minichromosome Maintenance Proteins
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