Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.
Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.
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DOI：
10.1111/cas.12551
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发表时间：
2014-12
期刊：
影响因子：
5.7
通讯作者：
Shinohara M
中科院分区：
文献类型：
--
作者：
Terasawa M;Shinohara A;Shinohara M
双链断裂（DSB）是最常见的DNA损伤类型之一。未修复的DSB容易诱导细胞死亡和染色体畸变。为了维持基因组的稳定性，细胞具有检查点和DSB修复系统，以在整个细胞周期的大部分时间内对DNA损伤做出反应。这一过程的失败通常导致细胞凋亡或基因组不稳定性，如非整倍性、缺失或易位。因此，DSB修复对于维持基因组稳定性至关重要。然而，在有丝分裂过程中，细胞似乎抑制了DNA损伤反应，并进入下一个G1期，即使存在未修复的DSB。这种抑制的生物学意义尚不清楚。本文就有丝分裂期DSB修复的研究进展进行综述，并对有丝分裂期DSB修复受到抑制的机制进行讨论。DSB修复在细胞周期的其他阶段维持基因组完整性，在有丝分裂期间对细胞具有相当大的毒性，通常导致染色体错误分离和畸变。细胞具有多种保护措施来防止有丝分裂期间的基因组不稳定性：抑制53BP1或BRCA1定位于DSB位点，这对于分别促进非同源末端连接或同源重组是重要的，并且还调节非同源末端连接核心复合物以抑制DSB修复。我们讨论了有丝分裂过程中DSB是如何有毒的，以及抑制基因组不稳定性的多重保障系统。
Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability.
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DOI：
10.4161/cc.20919
发表时间：
2012-07-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Gatti M;Pinato S;Maspero E;Soffientini P;Polo S;Penengo L
通讯作者：
Penengo L
影响因子：
11.4
作者：
Lee, Dong-Hyun;Goodarzi, Aaron A.;Chowdhury, Dipanjan
通讯作者：
Chowdhury, Dipanjan
影响因子：
16.8
作者：
Liu, Jie;Doty, Tammy;Heyer, Wolf-Dietrich
通讯作者：
Heyer, Wolf-Dietrich
影响因子：
4.8
作者：
Bishop, DK;Ear, U;Shinohara, A
通讯作者：
Shinohara, A
影响因子：
64.5
作者：
Doil, Carsten;Mailand, Niels;Lukas, Claudia
通讯作者：
Lukas, Claudia