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

Elaine M. Dunleavy; Alison L. Pidoux; Marie Monet; Carolina Bonilla; William Richardson; Georgina L. Hamilton; Karl Ekwall; Paul J. McLaughlin; Robin C. Allshire

doi:10.1016/j.molcel.2007.10.010

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

Elaine M. Dunleavy
, Alison L. Pidoux
, Marie Monet
, Carolina Bonilla
, William Richardson
, Georgina L. Hamilton
, Karl Ekwall
, Paul J. McLaughlin
, Robin C. Allshire

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

90 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1029-1044
Number of pages	16
Journal	Molecular Cell
Volume	28
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2007.10.010
Publication status	Published - 28 Dec 2007
Externally published	Yes

Keywords

DNA

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10.1016/j.molcel.2007.10.010

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

abstract = "A defining feature of centromeres is the presence of the histone H3 variant CENP-ACnp1. It is not known how CENP-ACnp1 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 NASPHuman and N1/N2Xenopus and aligns with Hif1S. cerevisiae, defining the SHNi-TPR family. Sim3 is distributed throughout the nucleoplasm, yet it associates with CENP-ACnp1 and also binds H3. Cells defective in Sim3 function have reduced levels of CENP-ACnp1 at centromeres (and increased H3) and display chromosome segregation defects. Sim3 is required to allow newly synthesized CENP-ACnp1 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-ACnp1 to chromatin assembly factors, allowing its incorporation into centromeric chromatin.",

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author = "Dunleavy, \{Elaine M.\} and Pidoux, \{Alison L.\} and Marie Monet and Carolina Bonilla and William Richardson and Hamilton, \{Georgina L.\} and Karl Ekwall and McLaughlin, \{Paul J.\} and Allshire, \{Robin C.\}",

year = "2007",

month = dec,

day = "28",

doi = "10.1016/j.molcel.2007.10.010",

language = "English",

volume = "28",

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journal = "Molecular Cell",

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T1 - A NASP (N1/N2)-Related Protein, Sim3, Binds CENP-A and Is Required for Its Deposition at Fission Yeast Centromeres

AU - Dunleavy, Elaine M.

AU - Pidoux, Alison L.

AU - Monet, Marie

AU - Bonilla, Carolina

AU - Richardson, William

AU - Hamilton, Georgina L.

AU - Ekwall, Karl

AU - McLaughlin, Paul J.

AU - Allshire, Robin C.

PY - 2007/12/28

Y1 - 2007/12/28

N2 - A defining feature of centromeres is the presence of the histone H3 variant CENP-ACnp1. It is not known how CENP-ACnp1 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 NASPHuman and N1/N2Xenopus and aligns with Hif1S. cerevisiae, defining the SHNi-TPR family. Sim3 is distributed throughout the nucleoplasm, yet it associates with CENP-ACnp1 and also binds H3. Cells defective in Sim3 function have reduced levels of CENP-ACnp1 at centromeres (and increased H3) and display chromosome segregation defects. Sim3 is required to allow newly synthesized CENP-ACnp1 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-ACnp1 to chromatin assembly factors, allowing its incorporation into centromeric chromatin.

AB - A defining feature of centromeres is the presence of the histone H3 variant CENP-ACnp1. It is not known how CENP-ACnp1 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 NASPHuman and N1/N2Xenopus and aligns with Hif1S. cerevisiae, defining the SHNi-TPR family. Sim3 is distributed throughout the nucleoplasm, yet it associates with CENP-ACnp1 and also binds H3. Cells defective in Sim3 function have reduced levels of CENP-ACnp1 at centromeres (and increased H3) and display chromosome segregation defects. Sim3 is required to allow newly synthesized CENP-ACnp1 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-ACnp1 to chromatin assembly factors, allowing its incorporation into centromeric chromatin.

KW - DNA

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U2 - 10.1016/j.molcel.2007.10.010

DO - 10.1016/j.molcel.2007.10.010

M3 - Article

SN - 1097-2765

VL - 28

SP - 1029

EP - 1044

JO - Molecular Cell

JF - Molecular Cell

IS - 6

ER -

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

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