A NASP (N1/N2)-Related Protein, Sim3, Binds CENP-A and Is Required for Its Deposition at Fission Yeast Centromeres

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• 作者：Elaine M. Dunleavy ; Alison L. Pidoux ; Marie Monet ; Carolina Bonilla ; William Richardson ; Georgina L. Hamilton ; Karl Ekwall ; Paul J. McLaughlin ; Robin C. Allshire
• 关键词：DNA
• 刊名：Molecular Cell
• 出版年：2007
• 出版时间：28 December 2007
• 年：2007
• 卷：28
• 期：6
• 页码：1029-1044
• 全文大小：1952 K

文摘

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.