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Chromosomes can't let go

A chromatin thread (green) stretches between anaphase chromatids (right). NIGG

Like lovers reluctant to part, sister chromatids prolong their physical attachment during mitosis, according to Christoph Baumann, Erich Nigg (Max Planck Institute of Biochemistry, Martinsried, Germany), and colleagues. The researchers observed previously unreported chromatin threads that tether separating chromatids until late in anaphase. By monitoring tension in the forming threads during metaphase, a protein called PICH might help to ensure that microtubules are correctly attached to the kinetochores.

Nigg and colleagues chanced on the filaments while hunting for proteins under the control of Polo-like kinase 1. This kinase strips off the cohesins that bind chromosome arms together and performs a variety of other tasks during mitosis. The protein they discovered, PICH, is a predicted helicase that congregates on the kinetochores and centromeres. To the team's surprise, it also adorns enigmatic threads that connect sister chromatids during metaphase and anaphase. The researchers suspect that these filaments are composed of catenated strands of centromeric chromatin. "The last connection between sister chromatids might be breaking much later than previously thought," says Nigg.

PICH is part of the spindle assembly checkpoint (SAC), which halts mitosis if the chromosomes aren't properly hitched to the mitotic spindle. When researchers depleted PICH with siRNA, for example, a SAC protein called Mad2 was lost from kinetochores, and two drugs that normally spur the SAC to block mitosis failed to work, indicating that the SAC was disabled.

PICH might help answer the long-standing question of how the SAC senses tension between sister kinetochores. If the kinetochores are correctly attached to microtubules, the tether will stretch as the sister chromatids are pulled in opposite directions. PICH could detect this change and signal the SAC to shut down, allowing mitosis to proceed. Topoisomerase enzymes would then decatenate the threads and permit the chromatids to finally part. To bolster the hypothesis, researchers now need to demonstrate that PICH responds to tension, says Nigg.

Reference:

Baumann, C., et al. 2007. Cell. 128:101–114.[CrossRef][Medline]

Mitch Leslie

mitchleslie{at}comcast.net

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This Article Full Text (PDF, 855K) 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 Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Social Bookmarking                            What's this?