Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 1137K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?

Kinetochore to order

Overproduced CENP-A (green) induces an ectopic kinetochore (blue) with attached microtubule (red). KARPEN/ELSEVIER

Extra functional kinetochores can be created by overexpressing just a single protein, according to Patrick Heun, Sylvia Erhardt, Gary Karpen (University of California, Berkeley, CA), and colleagues.

The protein, called CENP-A or, in flies, CID, makes sense as an initial foundation stone for kinetochores. It substitutes for histone H3 and thus, of all kinetochore proteins, gets closest to the DNA. Human tissue culture cells overexpressing CENP-A did not make extra kinetochores, possibly because of a shortage of other factors. But in fly cells the extra CENP-A incorporated into ectopic chromosomal sites and, at some of those sites, recruited inner and outer kinetochore proteins, and motor proteins. Microtubule connections at these sites appeared to be exerting force on the chromosomes and caused chromosome breaks and aneuploidy.

Additional factors may be needed to help define kinetochore identity, but "this tells us we are on the right track," says Karpen. He says evolution may have tolerated the occasional creation of new kinetochores because acentric products of chromosome rearrangments need a way to be rescued.

Karpen hopes to find sequences or histone modification patterns that favor either ectopic CENP-A incorporation or recruitment of other kinetochore proteins to these sites. The second challenge will be to find a loading factor specific for CENP-A, in the hope of localizing this factor and thus inducing kinetochore formation at a specific site.

Reference:

Heun, P., et al. 2006. Dev. Cell. 10:303–315.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF, 1137K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?