Arabidopsis MZT1 homologs GIP1 and GIP2 are essential for centromere architecture
Arabidopsis MZT1 homologs GIP1 and GIP2 are essential for centromere architecture
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DOI：
10.1073/pnas.1506351112
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发表时间：
2015-07-14
影响因子：
11.1
通讯作者：
Chaboute, Marie-Edith
中科院分区：
文献类型：
--
作者：
Batzenschlager, Morgane;Lermontova, Inna;Chaboute, Marie-Edith
着丝粒通过促进动粒和姐妹染色单体粘合蛋白的募集，在维持基因组完整性方面发挥着关键作用，这两种蛋白都是正确的染色体分离所必需的。着丝粒由组蛋白 H3 变体 (CENH3) 的存在进行表观遗传学指定。在这项研究中，我们研究了高度保守的 γ-微管蛋白复合蛋白 3 相互作用蛋白 (GIP) 在拟南芥着丝粒调节中的作用。我们发现 GIP 在循环细胞中与 CENH3 形成复合物。尽管着丝粒和异位位点均存在较高水平的 Mis18BP1/KNL2，但 gip1gip2 敲低突变体中的 GIP 耗尽导致着丝粒处的 CENH3 水平降低。因此，我们假设需要 GIP 来确保 CENH3 在着丝粒上的沉积和/或维持。此外，gip1gip2 中其他蛋白质（例如 CENP-C 着丝粒成分和粘连蛋白亚基 SMC3）在着丝粒处的募集受到损害。着丝粒结构中的这些缺陷由于着丝粒内聚力的严重改变而导致非整倍性。总而言之，我们认为 GIP 的核心功能是正确招募和/或稳定着丝粒蛋白，这对于着丝粒身份的规范以及体细胞中着丝粒的凝聚至关重要。
Centromeres play a pivotal role in maintaining genome integrity by facilitating the recruitment of kinetochore and sister-chromatid cohesion proteins, both required for correct chromosome segregation. Centromeres are epigenetically specified by the presence of the histone H3 variant (CENH3). In this study, we investigate the role of the highly conserved gamma-tubulin complex protein 3-interacting proteins (GIPs) in Arabidopsis centromere regulation. We show that GIPs form a complex with CENH3 in cycling cells. GIP depletion in the gip1gip2 knockdown mutant leads to a decreased CENH3 level at centromeres, despite a higher level of Mis18BP1/KNL2 present at both centromeric and ectopic sites. We thus postulate that GIPs are required to ensure CENH3 deposition and/or maintenance at centromeres. In addition, the recruitment at the centromere of other proteins such as the CENP-C kinetochore component and the cohesin subunit SMC3 is impaired in gip1gip2. These defects in centromere architecture result in aneuploidy due to severely altered centromeric cohesion. Altogether, we ascribe a central function to GIPs for the proper recruitment and/or stabilization of centromeric proteins essential in the specification of the centromere identity, as well as for centromeric cohesion in somatic cells.