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Checking in on spindle size

Cin8 expression causes DNA segregation (middle) and spindle elongation (right) during replication stalls. SURANA/ELSEVIER

Only replicated chromosomes should journey down mitotic spindles. The premature segregation of unreplicated DNA is prevented by the replication checkpoint, which is widely believed to block entry into mitosis when replication forks are stalled. But Vaidehi Krishnan, Uttam Surana, and colleagues (Institute of Molecular and Cell Biology, Singapore) show that the checkpoint has a more direct target—it prevents spindle elongation.

During replication stalls, budding yeast cells build short mitotic spindles. These spindles elongate in replication checkpoint-defective rad53 or mec1 mutants, thus causing untimely and uneven distribution of the DNA. Surana's group shows that this elongation occurs in the absence of most of the hallmarks of mitosis, including APC activation, cohesin cleavage, and biorientation.

"At least in early S phase, when cohesion and biorientation have not been established, cells are not looking ahead [to mitosis]," says Surana. "They are just solving a local problem of preserving nuclear integrity by preventing spindle elongation." Rad53 and Mec1 kinases accomplish this by down-regulating the microtubule-binding proteins Cin8 and Stu2, which elongate spindles. The microtubule destabilizing motor Kip3 also helped by restricting spindle elongation during synthesis delays.

Cin8 overexpression forced premature nuclear division in checkpoint-competent cells. Conversely, overexpression of Rad53 in cells whose DNA replicated normally resulted in abnormal and fragmented spindles.

Reference:

Krishnan, V., et al. 2004. Mol. Cell. 16:687–700.[CrossRef][Medline]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article Full Text (PDF, 280K) 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 LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?