一种与核仁酸性蛋白（NASP，N1/N2）相关的蛋白质Sim3，可结合着丝粒蛋白A（CENP-A），并且是其在裂殖酵母着丝粒上沉积所必需的。
A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres.
作者信息
Dunleavy Elaine M, Pidoux Alison L, Monet Marie, Bonilla Carolina, Richardson William, Hamilton Georgina L, Ekwall Karl, McLaughlin Paul J, Allshire Robin C
机构信息
Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, The University of Edinburgh, 6.34 Swann Building, Edinburgh EH9 3JR, Scotland, UK.
出版信息
Mol Cell. 2007 Dec 28;28(6):1029-44. doi: 10.1016/j.molcel.2007.10.010.
A defining feature of centromeres is the presence of the histone H3 variant CENP-A(Cnp1). It is not known how CENP-A(Cnp1) is specifically delivered to, and assembled into, centromeric chromatin. Through a screen for factors involved in kinetochore integrity in fission yeast, we identified Sim3. Sim3 is homologous to known histone binding proteins NASP(Human) and N1/N2(Xenopus) and aligns with Hif1(S. cerevisiae), defining the SHNi-TPR family. Sim3 is distributed throughout the nucleoplasm, yet it associates with CENP-A(Cnp1) and also binds H3. Cells defective in Sim3 function have reduced levels of CENP-A(Cnp1) at centromeres (and increased H3) and display chromosome segregation defects. Sim3 is required to allow newly synthesized CENP-A(Cnp1) to accumulate at centromeres in S and G2 phase-arrested cells in a replication-independent mechanism. We propose that one function of Sim3 is to act as an escort that hands off CENP-A(Cnp1) to chromatin assembly factors, allowing its incorporation into centromeric chromatin.
着丝粒的一个决定性特征是组蛋白H3变体CENP - A（Cnp1）的存在。目前尚不清楚CENP - A（Cnp1）是如何被特异性递送至着丝粒染色质并组装其中的。通过对裂殖酵母中动粒完整性相关因子的筛选，我们鉴定出了Sim3。Sim3与已知的组蛋白结合蛋白NASP（人类）和N1/N2（非洲爪蟾）同源，并且与Hif1（酿酒酵母）序列相似，从而定义了SHNi - TPR家族。Sim3分布于整个核质中，但它与CENP - A（Cnp1）相关联，并且也能结合H3。Sim3功能缺陷的细胞在着丝粒处CENP - A（Cnp1）水平降低（H3水平升高），并表现出染色体分离缺陷。Sim3是使新合成的CENP - A（Cnp1）以一种不依赖复制的机制在S期和G2期停滞的细胞的着丝粒处积累所必需的。我们提出，Sim3的一个功能是作为护送蛋白，将CENP - A（Cnp1）传递给染色质组装因子，使其整合进入着丝粒染色质。
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