Phosphorylation of CENP-R by Aurora B regulates kinetochore-microtubule attachment for accurate chromosome segregation.
Phosphorylation of CENP-R by Aurora B regulates kinetochore-microtubule attachment for accurate chromosome segregation.
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Aurora B 磷酸化 CENP-R 可调节动粒微管附着，以实现准确的染色体分离
DOI：
10.1093/jmcb/mjac051
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发表时间：
2022-09-27
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
无错误的有丝分裂依赖于染色体通过称为着丝粒的精细结构与纺锤体微管的精确连接，所述着丝粒由CENP-A核小体的富集在表观遗传学上指定。有丝分裂期间的着丝粒维持需要CENP-A介导的组成型着丝粒相关网络的沉积，该网络在有丝分裂期间建立内部动粒并将着丝粒染色质连接到纺锤体微管。虽然以前提出是视黄酸受体的适配器，在这里，我们表明，CENP-R协同CENP-OPQU调节着丝粒微管附着稳定性，并确保准确的染色体分离有丝分裂。我们发现CENP-R的磷酸化模拟突变减弱了其在动粒上的定位，表明磷酸化可能调节其定位。CENP-R磷酸化的扰动被证明可以阻止中期正确的着丝粒微管附着。从机制上讲，CENP-R磷酸化破坏了其与CENP-U的结合。因此，我们推测极光B介导的CENP-R磷酸化促进有丝分裂中不适当的着丝粒微管附着的纠正。由于CENP-R在酵母中不存在，我们推断后生动物进化出一种复杂的染色体稳定性控制机制，以确保有丝分裂中染色体的可靠分离。
Error-free mitosis depends on accurate chromosome attachment to spindle microtubules via a fine structure called the centromere that is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during mitosis requires CENP-A-mediated deposition of constitutive centromere-associated network that establishes the inner kinetochore and connects centromeric chromatin to spindle microtubules during mitosis. Although previously proposed to be an adaptor of retinoic acid receptor, here, we show that CENP-R synergizes with CENP-OPQU to regulate kinetochore–microtubule attachment stability and ensure accurate chromosome segregation in mitosis. We found that a phospho-mimicking mutation of CENP-R weakened its localization to the kinetochore, suggesting that phosphorylation may regulate its localization. Perturbation of CENP-R phosphorylation is shown to prevent proper kinetochore–microtubule attachment at metaphase. Mechanistically, CENP-R phosphorylation disrupts its binding with CENP-U. Thus, we speculate that Aurora B-mediated CENP-R phosphorylation promotes the correction of improper kinetochore–microtubule attachment in mitosis. As CENP-R is absent from yeast, we reasoned that metazoan evolved an elaborate chromosome stability control machinery to ensure faithful chromosome segregation in mitosis.
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影响因子：
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作者：
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