D'Ambrosio C, Kelly G, Shirahige K, Uhlmann F

The chromosomal condensin complex gives metaphase chromosomes structural stability. In addition, condensin is required for sister-chromatid resolution during their segregation in anaphase [1-7]. How condensin promotes chromosome resolution is poorly understood. Chromosome segregation during anaphase also fails after inactivation of topoisomerase II (topo II), the enzyme that removes catenation between ...

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sister chromatids left behind after completion of DNA replication [8, 9]. This has led to the proposal that condensin promotes DNA decatenation [3, 10, 11], but direct evidence for this is missing and alternative roles for condensin in chromosome resolution have been suggested [12-14]. Using the budding-yeast rDNA as a model, we now show that anaphase bridges in a condensin mutant are resolved by ectopic expression of a foreign (Chlorella virus) but not endogenous topo II. This suggests that catenation prevents sister-rDNA segregation but that yeast topo II is ineffective in decatenating the locus without condensin. Condensin and topo II colocalize along both rDNA and euchromatin, consistent with coordination of their activities. We investigate the physiological consequences of condensin-dependent rDNA decatenation and find that late decatenation determines the late segregation timing of this locus during anaphase. Regulation of decatenation therefore provides a means to fine tune the segregation timing of chromosomes in mitosis.

Date: Jul. 22, 2008

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