title: Physical Proximity of Sister Chromatids Promotes Top2-Dependent Intertwining.
abstract: Sister chromatid intertwines (SCIs), or catenanes, are topological links between replicated chromatids that interfere with chromosome segregation. The formation of SCIs is thought to be a consequence of fork swiveling during DNA replication, and their removal is thought to occur because of the intrinsic feature of type II topoisomerases (Top2) to simplify DNA topology. Here, we report that SCIs are also formed independently of DNA replication during G2/M by Top2-dependent concatenation of cohesed chromatids due to their physical proximity. We demonstrate that, in contrast to G2/M, Top2 removes SCIs from cohesed chromatids at the anaphase onset. Importantly, SCI removal in anaphase requires condensin and coincides with the hyperactivation of condensin DNA supercoiling activity. This is consistent with the longstanding proposal that condensin provides a bias in Top2 function toward decatenation. A comprehensive model for the formation and resolution of toxic SCI entanglements on eukaryotic genomes is proposed.
authors.affiliation: MRC Clinical Sciences Centre (CSC), Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Sen
authors.affiliation: MRC Clinical Sciences Centre (CSC), Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Leonard
authors.affiliation: MRC Clinical Sciences Centre (CSC), Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Raul
authors.initials: R
authors.lastname: Torres
authors.affiliation: MRC Clinical Sciences Centre (CSC), Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Jonay
authors.initials: J
authors.lastname: Garcia-Luis
authors.affiliation: MRC Clinical Sciences Centre (CSC), Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Gloria
authors.initials: G
authors.lastname: Palou-Marin
authors.affiliation: MRC Clinical Sciences Centre (CSC), Du Cane Road, London W12 0NN, UK; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, London W12 0NN, UK. Electronic address: luis.aragon@csc.mrc.ac.uk.
authors.forename: Luis
authors.initials: L
authors.lastname: Aragón
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000705:Anaphase; D002842:Chromatids / Q000378:metabolism / Q000648:ultrastructure; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000378:metabolism* / Q000648:ultrastructure; D004261:DNA Replication; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D015870:Gene Expression; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C108312:condensin complexes; D000251:Adenosine Triphosphatases; D004250:DNA Topoisomerases, Type II
keywords: DNA replication; SCI; Top2 (Topoisomerase 2); catenation; chromosome segregation; cohesin; condensin