Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin.,Nature Communications

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Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-24 , DOI: 10.1038/s41467-019-14276-x
Sreyoshi Mitra _{1,

2} , Dani L Bodor _{2,

3} , Ana F David _{2,

4} , Izma Abdul-Zani ₁ , João F Mata ₂ , Beate Neumann ₅ , Sabine Reither ₅ , Christian Tischer ₅ , Lars E T Jansen _{1,

2}

Affiliation

Centromeres are defined by a self-propagating chromatin structure based on stable inheritance of CENP-A containing nucleosomes. Here, we present a genetic screen coupled to pulse-chase labeling that allow us to identify proteins selectively involved in deposition of nascent CENP-A or in long-term transmission of chromatin-bound CENP-A. These include factors with known roles in DNA replication, repair, chromatin modification, and transcription, revealing a broad set of chromatin regulators that impact on CENP-A dynamics. We further identify the SUMO-protease SENP6 as a key factor, not only controlling CENP-A stability but virtually the entire centromere and kinetochore. Loss of SENP6 results in hyper-SUMOylation of CENP-C and CENP-I but not CENP-A itself. SENP6 activity is required throughout the cell cycle, suggesting that a dynamic SUMO cycle underlies a continuous surveillance of the centromere complex that in turn ensures stable transmission of CENP-A chromatin.

中文翻译：

基因筛查鉴定出动态维持着丝粒染色质的 SUMO 蛋白酶。

着丝粒由基于含有核小体的 CENP-A 稳定遗传的自我繁殖染色质结构定义。在这里，我们提出了一种与脉冲追踪标记相结合的遗传筛选，使我们能够选择性地识别参与新生 CENP-A 沉积或染色质结合 CENP-A 长期传输的蛋白质。其中包括在 DNA 复制、修复、染色质修饰和转录中具有已知作用的因子，揭示了影响 CENP-A 动态的一系列广泛的染色质调节因子。我们进一步确定 SUMO 蛋白酶 SENP6 是一个关键因素，它不仅控制 CENP-A 的稳定性，而且几乎控制整个着丝粒和着丝粒。 SENP6 的缺失会导致 CENP-C 和 CENP-I 的过度 SUMO 化，但不会导致 CENP-A 本身。 SENP6 活性在整个细胞周期中都是必需的，这表明动态 SUMO 循环是对着丝粒复合体持续监视的基础，从而确保 CENP-A 染色质的稳定传输。

更新日期：2020-01-24

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