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Published online before print December 30, 2003, 10.1101/gad.1150404
GENES & DEVELOPMENT 18:76-87, 2004
©2004 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH PAPER

In vivo requirements for rDNA chromosome condensation reveal two cell-cycle-regulated pathways for mitotic chromosome folding

Brigitte D. Lavoie1,3, Eileen Hogan2 and Doug Koshland2

1 Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada , 2 Department of Embryology, Howard Hughes Medical Institute, Carnegie Institution of Washington, Baltimore, Maryland 21210, USA

Chromosome condensation plays an essential role in the maintenance of genetic integrity. Using genetic, cell biological, and biochemical approaches, we distinguish two cell-cycle-regulated pathways for chromosome condensation in budding yeast. From G2 to metaphase, we show that the condensation of the ~1-Mb rDNA array is a multistep process, and describe condensin-dependent clustering, alignment, and resolution steps in chromosome folding. We functionally define a further postmetaphase chromosome assembly maturation step that is required for the maintenance of chromosome structural integrity during segregation. This late step in condensation requires the conserved mitotic kinase Ipl1/aurora in addition to condensin, but is independent of cohesin. Consistent with this, the late condensation pathway is initiated during the metaphase-to-anaphase transition, supports de novo condensation in cohesin mutants, and correlates with the Ipl1/aurora-dependent phosphorylation of condensin. These data provide insight into the molecular mechanisms of higher-order chromosome folding and suggest that two distinct condensation pathways, one involving cohesins and the other Ipl1/aurora, are required to modulate chromosome structure during mitosis.

[Keywords: Condensin; cohesin; mitotic chromosome structure; SMC proteins; IPL1/Aurora]

Received September 5, 2003; revised version accepted November 18, 2003.


Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1150404.

3 Corresponding author.

E-MAIL brigitte.lavoie{at}utoronto.ca; FAX (416) 978-6885.


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