A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast Centromeres

被引：86

作者：

Dunleavy, Elaine M. ^{[1
,2
]}

Pidoux, Alison L. ^{[1
,2
]}

Monet, Marie ^{[1
,2
]}

Bonilla, Carolina ^{[4
]}

Richardson, William ^{[5
]}

Hamilton, Georgina L. ^{[1
,2
]}

Ekwall, Karl ^{[4
]}

McLaughlin, Paul J. ^{[3
]}

Allshire, Robin C. ^{[1
,2
]}

机构：

[1] Univ Edinburgh, Sch Biol Sci, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland

[2] Univ Edinburgh, Sch Biol Sci, Inst Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland

[3] Univ Edinburgh, Sch Biol Sci, Inst Struct & Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland

[4] Karolinska Inst, Novum, Univ Coll Sodertorn, Dept Biosci & Med Nutr, S-14189 Huddinge, Sweden

[5] MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

来源：

MOLECULAR CELL | 2007年 / 28卷 / 06期

基金：

英国惠康基金;

关键词：

D O I：

10.1016/j.molcel.2007.10.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1029 / 1044

页数：16

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