DOI:10.1038/nrm2219

URLs

Links:Scm3

http://ca.expasy.org/uniprot/

Q12334

Cse4

http://ca.expasy.org/uniprot/

P36012

Ndc10

http://ca.expasy.org/uniprot/

P32504

The replacement of conventional histone H3 with an H3 variant in centromeric chromatin is thought to provide a structural basis for kinetochore assembly. But how centromere-specific nucleosome assembly and kinetochore formation are linked has been unclear. Three recent studies report the identi-fication of the non-histone Scm3 protein, which is important for the recruitment to, and assembly of, the histone H3 variant Cse4 into centro-meric chromatin in budding yeast. Surprisingly, the core histones H2A and H2B are missing from centro-meric chromatin, whereas Cse4 and Scm3 and histone H4 remain.

Mizuguchi et al. and Camahort et al. isolated Scm3 from an immuno-purified Cse4 fraction. Scm3

immuno precipitated with Cse4 and vice versa, but not with histone H3. Scm3 was also identified by Stoler et al. by screening for dosage sup-pressors of a conditional cse4 allele. Chromatin immunoprecipitation studies by all groups revealed that Scm3 localizes specifically to centro-meres. Using conditional mutants of Scm3 and Cse4, these groups also demonstrated that Cse4 and Scm3 depend on each other for localization to the centromere, which implied that Scm3 is required for centromere formation.

In addition, Camahort et al. showed that Scm3 co-immuno-precipitates with the kinetochore protein Ndc10, which is required for Scm3 localization to centromeres. Conversely, Scm3 is essential for the centromeric binding of several kine-tochore proteins, including Ndc10, which is thought to be the first kine-tochore protein that localizes to the centromere and initiates kinetochore formation. Because of the physical association between Scm3 and Ncd10, the authors suggest that Scm3 might be the ‘missing link’ that con-nects Ndc10-mediated kinetochore formation with the recruitment of Cse4 to the centromere.

So what is the significance of Scm3 for kinetochore function? All groups showed that Scm3 depletion results in G2–M cell-cycle arrest and chromosome segregation defects — these phenotypes are consistent with defects in kinetochore function. In addition, Camahort et al. and Stoler et al. showed that Scm3 is required

to maintain kinetochore function throughout the cell cycle, which prompted the proposal that Scm3 might help to recruit kinetochore proteins other than Ndc10, and/or that Scm3 is essential for the continu-ous loading of Ndc10 that is required to maintain a segregation-competent kinetochore.

Mizuguchi et al. made the star-tling observation that centromeric chromatin contains Cse4 and Scm3 but lacks the histones H2A and H2B in vivo. Bacterially expressed Scm3 formed a stoichiometric complex with Cse4 and H4 in vitro. Even more strikingly, when Scm3 was added to pre-assembled Cse4-containing histone octamers in vitro, it replaced H2A–H2B from the complex. This incompatibility correlates with the reduced in vivo occupancy of his-tones H2A and H2B, relative to H4, at centromeres in a scm3 conditional strain under permissive conditions. It will be interesting now to look at the nucleosome packaging of cen-tromeric DNA in higher organisms — who knows what surprises other specialized nucleosome packages have in store.

Arianne Heinrichs

ORIGINAL RESEARCH PAPERS Mizuguchi, G.

et al. Nonhistone Scm3 and histones CenH3-H4

assemble the core of centromere-specific

nucleosomes. Cell 129, 1153–1164 (2007) |

Camahort, R. et al. Scm3 is essential to recruit the

histone H3 variant Cse4 to centromeres and to

maintain a functional kinetochore. Mol. Cell 26,

853–865 (2007) | Stoler, S. et al. Scm3, an essential

Saccharomyces cerevisiae centromere protein

required for G2/M progression and Cse4

localization. Proc. Natl Acad. Sci. USA 104,

10571–10576 (2007)

C H R O M AT I N

A surprise package

…who knows what surprises other specialized nucleosome packages have in store.

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R E S E A R C H H I G H L I G H T S

NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 8 | AUGUST 2007

Nature Reviews Molecular Cell Biology | AOP, published online 4 July 2007; doi:10.1038/nrm2219

© 2007 Nature Publishing Group