Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, 75005, Paris, France.
Department of Genetic Stability and Oncogenesis, Institut Gustave Roussy, CNRS UMR8200, 94805, Villejuif, France.
Nat Commun. 2019 Jan 11;10(1):175. doi: 10.1038/s41467-018-08073-1.
CENP-A is the histone H3 variant necessary to specify the location of all eukaryotic centromeres via its CENP-A targeting domain and either one of its terminal regions. In humans, several post-translational modifications occur on CENP-A, but their role in centromere function remains controversial. One of these modifications of CENP-A, phosphorylation on serine 7, has been proposed to control centromere assembly and function. Here, using gene targeting at both endogenous CENP-A alleles and gene replacement in human cells, we demonstrate that a CENP-A variant that cannot be phosphorylated at serine 7 maintains correct CENP-C recruitment, faithful chromosome segregation and long-term cell viability. Thus, we conclude that phosphorylation of CENP-A on serine 7 is dispensable to maintain correct centromere dynamics and function.
着丝粒蛋白 A（CENP-A）是一种组蛋白 H3 变体，通过其着丝粒蛋白 A 靶向结构域和其两个末端区域之一，指定所有真核生物着丝粒的位置。在人类中，CENP-A 发生了几种翻译后修饰，但它们在着丝粒功能中的作用仍存在争议。CENP-A 的一种修饰形式，丝氨酸 7 的磷酸化，被认为可以控制着丝粒的组装和功能。在这里，我们通过内源性 CENP-A 等位基因的基因靶向和人细胞中的基因替换，证明了一种不能在丝氨酸 7 处磷酸化的 CENP-A 变体能够维持正确的 CENP-C 募集、忠实的染色体分离和长期细胞活力。因此，我们得出结论，丝氨酸 7 上 CENP-A 的磷酸化对于维持正确的着丝粒动力学和功能是可有可无的。
