Proliferative potential after DNA damage and non-homologous end joining are affected by loss of securin
Proliferative potential after DNA damage and non-homologous end joining are affected by loss of securin
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DOI：
10.1038/sj.cdd.4402254
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发表时间：
2008-01-01
影响因子：
12.4
通讯作者：
Pintor-Toro, J. A.
中科院分区：
文献类型：
--
作者：
Bernal, J. A.;Roche, M.;Pintor-Toro, J. A.
DNA损伤，特别是染色体双链断裂（DSB）的忠实修复对基因组完整性至关重要。我们以前已经表明，securin相互作用的Ku 70/80异二聚体的DSB非同源DNA末端连接（NHEJ）修复机制。在这里，我们表明，安全蛋白缺乏损害细胞的生存和增殖，但只有在基因毒性应激。Securin（-/-）细胞显示DNA损伤后总染色体重排和染色单体断裂显著增加，并且还揭示了与securin（+/+）细胞相比在NHEJ测定中末端切除的改变模式。这些数据表明，securin在DNA损伤后维持基因组稳定性方面具有关键作用，从而提供了一种以前未知的调节肿瘤进展的机制。
aThe faithful repair of DNA damage, especially chromosomal double-strand breaks (DSBs), is crucial for genomic integrity. We have previously shown that securin interacts with the Ku70/80 heterodimer of the DSB non-homologous DNA end-joining (NHEJ) repair machinery. Here we demonstrate that securin deficiency compromises cell survival and proliferation, but only after genotoxic stress. Securin(-/-) cells show a significant increase in gross chromosomal rearrangements and chromatid breaks after DNA damage, and also reveal an altered pattern of end resection in an NHEJ assay in comparison with securin(+/+) cells. These data suggest that securin has a key role in the maintenance of genomic stability after DNA damage, thereby providing a previously unknown mechanism for regulating tumour progression.