Molecular Cell
Volume 75, Issue 1, 11 July 2019, Pages 131-144.e3
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Article
Condensin-Mediated Chromosome Folding and Internal Telomeres Drive Dicentric Severing by Cytokinesis

https://doi.org/10.1016/j.molcel.2019.05.021Get rights and content
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Highlights

  • Rap1 and condensin promote dicentric breakage at telomere fusions

  • Condensin refolds stretched dicentric bridges prior to their breakage by septation

  • Breakage hotspots result from a higher chance of being entrapped at the abscission site

  • Rap1 bound in tandem with close spacing may stall condensin by steric hindrance

Summary

In Saccharomyces cerevisiae, dicentric chromosomes stemming from telomere fusions preferentially break at the fusion. This process restores a normal karyotype and protects chromosomes from the detrimental consequences of accidental fusions. Here, we address the molecular basis of this rescue pathway. We observe that tandem arrays tightly bound by the telomere factor Rap1 or a heterologous high-affinity DNA binding factor are sufficient to establish breakage hotspots, mimicking telomere fusions within dicentrics. We also show that condensins generate forces sufficient to rapidly refold dicentrics prior to breakage by cytokinesis and are essential to the preferential breakage at telomere fusions. Thus, the rescue of fused telomeres results from a condensin- and Rap1-driven chromosome folding that favors fusion entrapment where abscission takes place. Because a close spacing between the DNA-bound Rap1 molecules is essential to this process, Rap1 may act by stalling condensins.

Keywords

Telomere
condensing
SMC
yeast
mitosis
telophase
abscission
mutagenesis
Hi-C
lacI

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