Mitotic UV irradiation induces a DNA replication-licensing defect that potentiates G1 arrest response.
Mitotic UV irradiation induces a DNA replication-licensing defect that potentiates G1 arrest response.
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DOI：
10.1371/journal.pone.0120553
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nishitani H
中科院分区：
文献类型：
--
作者：
Morino M;Nukina K;Sakaguchi H;Maeda T;Takahara M;Shiomi Y;Nishitani H
CDT1在M期开始积累，并在有丝分裂结束或G1期早期建立复制许可中起关键作用。损伤细胞DNA的处理，如紫外线照射，通过依赖于增殖细胞核抗原的CRL4-CDT2泛素连接酶诱导CDT1降解。然而，CDT1降解是如何与细胞周期进程联系在一起的，目前还不清楚。在G1阶段，当许可建立时，紫外光照射会导致Cdt1的降解，但对许可状态几乎没有影响。然而，在M期，紫外光照射不会引起Cdt1的降解。当有丝分裂的紫外线照射的细胞被释放到G1期时，CDT1在许可建立之前就被降解了。因此，这些细胞既表现出许可缺陷，又表现出G1期停滞。在表达额外拷贝的CDT2的细胞中，G1停滞的频率增加，因此在CDT1降解增强的细胞中，G1停滞的频率增加，而在表达额外拷贝的CDT1的细胞中，G1停滞的频率降低。细胞在有丝分裂过程中受到照射后的G1期停滞反应，通过阻止细胞凋亡的诱导，对细胞存活具有重要意义。基于这些观察，我们认为哺乳动物细胞对有丝分裂过程中诱导的DNA损伤具有DNA复制许可检查点反应。
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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DOI：
10.1073/pnas.0603779103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Marti, Thomas M.;Hefner, Eli;Cleaver, James E.
通讯作者：
Cleaver, James E.
DOI：
10.4161/cc.8.1.7528
发表时间：
2009-01-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Liu P;Slater DM;Lenburg M;Nevis K;Cook JG;Vaziri C
通讯作者：
Vaziri C
影响因子：
16
作者：
Miotto B;Struhl K
通讯作者：
Struhl K
DOI：
10.1038/nrm1663
发表时间：
2005-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ