Biphasic incorporation of centromeric histone CENP-A in fission yeast
Biphasic incorporation of centromeric histone CENP-A in fission yeast
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DOI：
10.1091/mbc.e07-05-0504
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发表时间：
2008-02-01
影响因子：
3.3
通讯作者：
Takahashi, Kohta
中科院分区：
文献类型：
--
作者：
Takayama, Yuko;Sato, Hiroshi;Takahashi, Kohta
CENP-A是着丝粒特异的组蛋白H3变体，对着丝粒的形成是必不可少的。在这里，我们报道了裂解酵母在整个细胞周期中至少有两个不同的CENP-A沉积阶段：S和G2。S时相沉积需要Ams2 GATA因子，促进组蛋白基因激活。在Delta ams2中，CENP-A在S期间未能保留，但它通过G2沉积途径重新聚集到着丝粒上，该途径被HIRA组蛋白伴侣的同系物Hip1下调。在Delta ams2中，缩短G2的长度会导致CENP-A积累失败，导致染色体错误分离。N-末端绿色荧光蛋白标记减少了CENP-A的着丝粒结合，导致了Delta ams2的细胞死亡，但对野生型细胞没有影响，这表明CENP-A的N末端尾部可能在G2的着丝粒核小体的形成中发挥了关键作用。这些观察结果表明，CENP-A通常以Ams2依赖的方式定位在S期的着丝粒上，G2途径可能挽救CENP-A的组装，促进基因组的稳定。CENP-A在细胞周期中掺入的灵活性可能解释了当着丝粒受损时动粒形成的可塑性。
CENP-A is a centromere-specific histone H3 variant that is essential for kinetochore formation. Here, we report that the fission yeast Schizosaccharomyces pombe has at least two distinct CENP-A deposition phases across the cell cycle: S and G2. The S phase deposition requires Ams2 GATA factor, which promotes histone gene activation. In Delta ams2, CENP-A fails to retain during S, but it reaccumulates onto centromeres via the G2 deposition pathway, which is down-regulated by Hip1, a homologue of HIRA histone chaperon. Reducing the length of G2 in Delta ams2 results in failure of CENP-A accumulation, leading to chromosome missegregation. N-terminal green fluorescent protein-tagging reduces the centromeric association of CENP-A, causing cell death in Delta ams2 but not in wild-type cells, suggesting that the N-terminal tail of CENP-A may play a pivotal role in the formation of centromeric nucleosomes at G2. These observations imply that CENP-A is normally localized to centromeres in S phase in an Ams2-dependent manner and that the G2 pathway may salvage CENP-A assembly to promote genome stability. The flexibility of CENP-A incorporation during the cell cycle may account for the plasticity of kinetochore formation when the authentic centromere is damaged.