Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin
Fully functional global genome repair of (6-4) photoproducts and compromised transcription-coupled repair of cyclobutane pyrimidine dimers in condensed mitotic chromatin
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DOI：
10.1016/j.yexcr.2012.01.003
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发表时间：
2012-03-10
影响因子：
3.7
通讯作者：
Ono, Tetsuya
中科院分区：
文献类型：
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作者：
Komura, Jun-ichiro;Ikehata, Hironobu;Ono, Tetsuya
在有丝分裂过程中，染色质高度浓缩，不发生转录和保守复制等活动。因此，有丝分裂染色质的浓缩状态被认为通过阻碍DNA反式作用蛋白的进入来抑制DNA代谢。然而，大约40年前，一些研究人员在紫外线照射的有丝分裂染色体中观察到非程序性DNA合成，表明存在切除修复。我们重新审视这个问题，直接测量去除紫外线诱导的DNA损伤的ELISA和基于南方的技术在HeLa细胞有丝分裂被捕。我们观察到，在有丝分裂细胞中从整个基因组中去除（6-4）光产物与在间期细胞中一样有效。这表明（6-4）光产物的整体基因组修复在有丝分裂期间是完全功能性的，并且有丝分裂染色质中的DNA可接近参与这种DNA修复模式的蛋白质。然而，并不是所有的DNA修复模式在有丝分裂过程中都发挥了作用。我们还观察到，在有丝分裂细胞中，从二氢叶酸还原酶和c-MYC基因中去除环丁烷嘧啶二聚体非常缓慢。这表明环丁烷嘧啶二聚体的转录偶联修复在有丝分裂期间受损或无功能，这可能是有丝分裂转录抑制的结果。(C)2012 Elsevier Inc. All rights reserved.
During mitosis, chromatin is highly condensed, and activities such as transcription and semiconservative replication do not occur. Consequently, the condensed condition of mitotic chromatin is assumed to inhibit DNA metabolism by impeding the access of DNA-transacting proteins. However, about 40 years ago, several researchers observed unscheduled DNA synthesis in UV-irradiated mitotic chromosomes, suggesting the presence of excision repair. We re-examined this subject by directly measuring the removal of UV-induced DNA lesions by an ELISA and by a Southern-based technique in HeLa cells arrested at mitosis. We observed that the removal of (6-4) photoproducts from the overall genome in mitotic cells was as efficient as in interphase cells. This suggests that global genome repair of (6-4) photoproducts is fully functional during mitosis, and that the DNA in mitotic chromatin is accessible to proteins involved in this mode of DNA repair. Nevertheless, not all modes of DNA repair seem fully functional during mitosis. We also observed that the removal of cyclobutane pyrimidine dimers from the dihydrofolate reductase and c-MYC genes in mitotic cells was very slow. This suggests that transcription-coupled repair of cyclobutane pyrimidine dimers is compromised or non-functional during mitosis, which is probably the consequence of mitotic transcriptional repression. (C) 2012 Elsevier Inc. All rights reserved.