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Chromosome length and perinuclear attachment constrain resolution of DNA intertwines Titos Vivancos, Iris Ivanova, Tsvetomira Georgieva, 1978- Mendoza, Manuel (Mendoza Palomares) Cromosomes -- Anàlisi Genètica ADN To allow chromosome segregation, topoisomerase II (topo II) must resolve sister chromatid intertwines (SCI) formed during deoxynucleic acid (DNA) replication. How this process extends to the full genome is not well understood. In budding yeast, the unique structure of the ribosomal DNA (rDNA) array is thought to cause late SCI resolution of this genomic region during anaphase. In this paper, we show that chromosome length, and not the presence of rDNA repeats, is the critical feature determining the time of topo II–dependent segregation. Segregation of chromosomes lacking rDNA also requires the function of topo II in anaphase, and increasing chromosome length aggravates missegregation in topo II mutant cells. Furthermore, anaphase Stu2-dependent microtubule dynamics are critical for separation of long chromosomes. Finally, defects caused by topo II or Stu2 impairment depend on attachment of telomeres to the nuclear envelope. We propose that topological constraints imposed by chromosome length and perinuclear attachment determine the amount of SCI that topo II and dynamic microtubules resolve during anaphase. We thank Pedro Carvalho, Snezhana Oliferenko, and Steven Gross for critical reading of the manuscript; Francesc Posas, Fèlix Campelo, Jordi Torres, Yves Barral, and Susan Gasser for helpful suggestions; Trinidad Sanmartín for technical support; the Centre for Genomic Regulation Genomics, Bioinformatics, and Advanced Light Microscopy Units; and the Institut de Recerca Biomèdica Advanced Digital Microscopy Facility. This research is supported by grants from the European Research Council (ERC Starting Grant 260965) and the Spanish Ministry of Science (BFU09-08213) to M. Mendoza. The authors declare no competing financial interests. 2024-10-21T06:29:26Z 2024-10-21T06:29:26Z 2014 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Journal of Cell Biology. 2014 Sep 15;206(6):719-33 info:eu-repo/grantAgreement/EC/FP7/260965 info:eu-repo/grantAgreement/ES/1PE/BFU09-08213 © 2014 Titos et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). http://creativecommons.org/licenses/by-nc-sa/3.0/ info:eu-repo/semantics/openAccess Rockefeller University Press