Posttranslational modifications of CENP-A: marks of distinction.

Posttranslational modifications of CENP-A: marks of distinction.
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DOI:
10.1007/s00412-018-0665-x
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发表时间:
2018-09
期刊:
影响因子:
1.6
通讯作者:
Foltz DR
Foltz DR
中科院分区:
生物学3区
文献类型:
--
作者:
Srivastava S;Foltz DR

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着丝粒是一种特殊的染色体结构域,在细胞分裂过程中作为着丝粒组装和微管附着的位点,以确保染色体的正确分离。在高等真核生物中,活性着丝粒的身份是由CENP-A(着丝粒蛋白-A),一种组蛋白H3变体的存在来标记的。CENP-A形成着丝粒特异性核小体,其充当着丝粒组装和功能的基础。组蛋白的翻译后修饰(PTM)是调控染色质功能的主要机制。虽然一些CENP-A位点特异性修饰与组蛋白H3共享,但大多数对含有CENP-A的核小体具有特异性,表明这些残基的修饰有助于着丝粒特异性功能。CENP-A经历翻译后修饰,包括磷酸化、乙酰化、甲基化和泛素化。来自许多实验室的工作已经揭示了这些CENP-A修饰在其在着丝粒处的沉积、蛋白质稳定性和CCAN(组成性着丝粒相关网络)的募集中的重要性。在这里,我们讨论了CENP-A的PTM及其生物学相关性。
Centromeres are specialized chromosome domain that serve as the site for kinetochore assembly and microtubule attachment during cell division, to ensure proper segregation of chromosomes. In higher eukaryotes, the identity of active centromeres is marked by the presence of CENP-A (centromeric protein-A), a histone H3 variant. CENP-A forms a centromere-specific nucleosome that acts as a foundation for centromere assembly and function. The posttranslational modification (PTM) of histone proteins is a major mechanism regulating the function of chromatin. While a few CENP-A site-specific modifications are shared with histone H3, the majority are specific to CENP-A-containing nucleosomes, indicating that modification of these residues contribute to centromere-specific function. CENP-A undergoes posttranslational modifications including phosphorylation, acetylation, methylation, and ubiquitylation. Work from many laboratories have uncovered the importance of these CENP-A modifications in its deposition at centromeres, protein stability, and recruitment of the CCAN (constitutive centromere-associated network). Here, we discuss the PTMs of CENP-A and their biological relevance.
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