HJURP Is a Cell-Cycle-Dependent Maintenance and Deposition Factor of CENP-A at Centromeres
HJURP Is a Cell-Cycle-Dependent Maintenance and Deposition Factor of CENP-A at Centromeres
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DOI：
10.1016/j.cell.2009.02.040
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发表时间：
2009-05-01
期刊：
影响因子：
64.5
通讯作者：
Almouzni-Pettinotti, Genevieve
中科院分区：
文献类型：
--
作者：
Dunleavy, Elaine M.;Roche, Daniele;Almouzni-Pettinotti, Genevieve
组蛋白H3变体CenH 3，在人类中称为CENP-A，是着丝粒染色质的中心，以确保正确的染色体分离。在缺乏潜在的DNA序列的情况下，仍然不清楚CENP-A在着丝粒处的沉积是如何确定的。在这里，我们纯化了非核小体CENP-A复合物，以鉴定参与这种机制的直接CENP-A伴侣，并鉴定了HJURP。在含H3.1或H3.3的复合物中未检测到HJURP，表明其对CENP-A的特异性。HJURP着丝粒定位受细胞周期调节，并且其在着丝粒处的瞬时出现与新CENP-A沉积的所提出的时间窗精确地一致。此外，HJURP下调导致着丝粒处CENP-A的大量减少，并损害新合成的CENP-A的沉积，导致有丝分裂缺陷。我们的结论是，HJURP是CENP-A沉积和维持在着丝粒的关键因素。
The histone H3 variant CenH3, called CENP-A in humans, is central in centromeric chromatin to ensure proper chromosome segregation. In the absence of an underlying DNA sequence, it is still unclear how CENP-A deposition at centromeres is determined. Here, we purified non-nucleosomal CENP-A complexes to identify direct CENP-A partners involved in such a mechanism and identified HJURP. HJURP was not detected in H3.1- or H3.3-containing complexes, indicating its specificity for CENP- A. HJURP centromeric localization is cell cycle regulated, and its transient appearance at the centromere coincides precisely with the proposed time window for new CENP- A deposition. Furthermore, HJURP downregulation leads to a major reduction in CENP-A at centromeres and impairs deposition of newly synthesized CENP-A, causing mitotic defects. We conclude that HJURP is a key factor for CENP-A deposition and maintenance at centromeres.