title: Mitotic UV irradiation induces a DNA replication-licensing defect that potentiates G1 arrest response.
abstract: 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.
authors: Graduate School of Life Science, University of Hyogo, Kamigori, Ako-gun, Hyogo, Japan.
authors: Masayuki
authors: M
authors: Morino
authors: Graduate School of Life Science, University of Hyogo, Kamigori, Ako-gun, Hyogo, Japan.
authors: Kohei
authors: K
authors: Nukina
authors: Graduate School of Life Science, University of Hyogo, Kamigori, Ako-gun, Hyogo, Japan.
authors: Hiroki
authors: H
authors: Sakaguchi
authors: Graduate School of Life Science, University of Hyogo, Kamigori, Ako-gun, Hyogo, Japan.
authors: Takeshi
authors: T
authors: Maeda
authors: Graduate School of Life Science, University of Hyogo, Kamigori, Ako-gun, Hyogo, Japan.
authors: Michiyo
authors: M
authors: Takahara
authors: Graduate School of Life Science, University of Hyogo, Kamigori, Ako-gun, Hyogo, Japan.
authors: Yasushi
authors: Y
authors: Shiomi
authors: Graduate School of Life Science, University of Hyogo, Kamigori, Ako-gun, Hyogo, Japan.
authors: Hideo
authors: H
authors: Nishitani
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics; D004261:DNA Replication / Q000528:radiation effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics* / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics* / Q000528:radiation effects*; D009687:Nuclear Proteins / Q000378:metabolism; D055550:Protein Stability / Q000528:radiation effects; D059748:Proteolysis / Q000528:radiation effects; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; C429530:DTL protein, human; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; D064110:Minichromosome Maintenance Proteins