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中靶素在细胞对 DNA 损伤的反应中发挥作用。

Centrobin plays a role in the cellular response to DNA damage.

机构信息

Department of Pharmacology, Chonnam National University Medical School , Jellanamdo , Republic of Korea.

出版信息

Cell Cycle. 2019 Oct;18(20):2660-2671. doi: 10.1080/15384101.2019.1654796. Epub 2019 Aug 15.

Abstract

DNA repair proteins have been found to localize to the centrosomes and defects in these proteins cause centrosome abnormality. Centrobin is a centriole-associated protein that is required for centriole duplication and microtubule stability. A recent study revealed that centrobin is a candidate substrate for ATM/ATR kinases. However, whether centrobin is involved in DNA damage response (DDR) remains unexplored. Here we show that centrobin is phosphorylated after UV exposure and that the phosphorylation is detected exclusively in the detergent/DNase I-resistant nuclear matrix. UV-induced phosphorylation of centrobin is largely dependent on ATR activity. Centrobin-depleted cells show impaired DNA damage-induced microtubule stabilization and increased sensitivity to UV radiation. Interestingly, depletion of centrobin leads to defective homologous recombination (HR) repair, which is reversed by expression of wild-type centrobin. Taken together, these results strongly suggest that centrobin plays an important role in DDR.

摘要

已发现 DNA 修复蛋白定位于中心体,这些蛋白的缺陷会导致中心体异常。Centrobin 是一种与中心粒相关的蛋白,对于中心粒的复制和微管的稳定性是必需的。最近的一项研究表明,Centrobin 是 ATM/ATR 激酶的候选底物。然而,Centrobin 是否参与 DNA 损伤反应 (DDR) 仍未被探索。在这里,我们显示 Centrobim 在 UV 暴露后发生磷酸化,并且这种磷酸化仅在去污剂/DNase I 抗性核基质中检测到。UV 诱导的 Centrobim 磷酸化在很大程度上依赖于 ATR 活性。Centrobin 耗竭细胞显示出受损的 DNA 损伤诱导的微管稳定和对 UV 辐射的敏感性增加。有趣的是,Centrobin 的耗竭导致同源重组 (HR) 修复缺陷,而野生型 Centrobin 的表达可逆转这种缺陷。总之,这些结果强烈表明 Centrobim 在 DDR 中发挥重要作用。

相似文献

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Centrobin plays a role in the cellular response to DNA damage.中靶素在细胞对 DNA 损伤的反应中发挥作用。
Cell Cycle. 2019 Oct;18(20):2660-2671. doi: 10.1080/15384101.2019.1654796. Epub 2019 Aug 15.
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NEK2 phosphorylation antagonizes the microtubule stabilizing activity of centrobin.NEK2 磷酸化拮抗中心体结合蛋白的微管稳定活性。
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本文引用的文献

1
ATR-mediated regulation of nuclear and cellular plasticity.ATR介导的核与细胞可塑性调控。
DNA Repair (Amst). 2016 Aug;44:143-150. doi: 10.1016/j.dnarep.2016.05.020. Epub 2016 May 16.
2
Centrosome function and assembly in animal cells.动物细胞中心体的功能和组装。
Nat Rev Mol Cell Biol. 2015 Oct;16(10):611-24. doi: 10.1038/nrm4062. Epub 2015 Sep 16.
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DNA double-strand break repair in a cellular context.细胞环境中的DNA双链断裂修复
Clin Oncol (R Coll Radiol). 2014 May;26(5):243-9. doi: 10.1016/j.clon.2014.02.004. Epub 2014 Mar 11.
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Association of nucleus and centrosome: magnet or velcro?核与中心体的关联:磁体还是魔术贴?
Cell Biol Int. 2013 Feb;37(2):95-104. doi: 10.1002/cbin.10016. Epub 2013 Jan 2.
9
NEK2 phosphorylation antagonizes the microtubule stabilizing activity of centrobin.NEK2 磷酸化拮抗中心体结合蛋白的微管稳定活性。
Biochem Biophys Res Commun. 2013 Feb 8;431(2):302-8. doi: 10.1016/j.bbrc.2012.12.106. Epub 2013 Jan 3.
10
Cell cycle regulation by the NEK family of protein kinases.NEK 家族蛋白激酶对细胞周期的调控。
J Cell Sci. 2012 Oct 1;125(Pt 19):4423-33. doi: 10.1242/jcs.111195. Epub 2012 Nov 6.

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