Coilin和SUMOylation影响PARP1动力学和DNA损伤反应。

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Journal of cell science Pub Date : 2025-05-15 Epub Date: 2025-05-21 DOI:10.1242/jcs.263953
Sara K Tucker, Blaise C Seale, David T Brown, Michael D Hebert
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引用次数: 0

摘要

Coilin是一种核质蛋白,在Cajal小体(CB)的某些细胞类型中富集。CBs参与许多不同类型的核糖核蛋白(RNPs)的生物发生,如小核RNPs。Coilin被称为CB标记蛋白,是CB形成所必需的。核质卷曲蛋白的功能尚不清楚,并且已被证明影响SUMO(小的泛素样修饰物)对蛋白质的修饰。此外,卷曲蛋白被招募到由UVA暴露或单纯疱疹病毒蛋白表达引起的DNA损伤部位。PARP1是一种DNA损伤反应蛋白,已被PIAS4(一种与卷曲蛋白相关的SUMO E3连接酶)sumo化。在这里,我们发现当卷曲蛋白被抑制时,PARP1的SUMOylation减少。我们还发现,coilin敲低和SUMO抑制剂药物TAK-981会影响PARP1对微辐照的反应动力学。此外,coilin的SUMOylation状态影响其在CB中的迁移和DNA损伤位点的招募。这些数据表明,coilin和SUMOylation都对DNA损伤反应有影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Coilin and SUMOylation influence PARP1 dynamics and the DNA damage response.

Coilin is a nucleoplasmic protein that is enriched in some cell types in the Cajal body (CB). CBs take part in the biogenesis of many different types of ribonucleoproteins (RNPs), such as small nuclear RNPs. Coilin is known as the CB marker protein and is required for CB formation. The function of nucleoplasmic coilin is less understood and has been shown to impact protein modification by SUMO, the small ubiquitin-like modifier. Additionally, it is known that coilin is recruited to sites of DNA damage caused by UVA exposure or expression of herpes simplex viral protein. PARP1, a DNA damage response protein, has been shown to be SUMOylated by PIAS4, a SUMO E3 ligase that associates with coilin. Here, we show that SUMOylation of PARP1 is lessened when coilin is suppressed. We also found that coilin knockdown and a SUMO inhibitor drug, TAK-981, influence the dynamics of PARP1 in response to micro-irradiation. Additionally, we find that the SUMOylation status of coilin influences its mobility in the CB and recruitment to sites of DNA damage. These data demonstrate that coilin and SUMOylation both have an influence on the DNA damage response.

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来源期刊
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
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