title: Genome-organizing factors Top2 and Hmo1 prevent chromosome fragility at sites of S phase transcription.
abstract: Specialized topoisomerases solve the topological constraints arising when replication forks encounter transcription. We have investigated the contribution of Top2 in S phase transcription. Specifically in S phase, Top2 binds intergenic regions close to transcribed genes. The Top2-bound loci exhibit low nucleosome density and accumulate gammaH2A when Top2 is defective. These intergenic loci associate with the HMG protein Hmo1 throughout the cell cycle and are refractory to the histone variant Htz1. In top2 mutants, Hmo1 is deleterious and accumulates at pericentromeric regions in G2/M. Our data indicate that Top2 is dispensable for transcription and that Hmo1 and Top2 bind in the proximity of genes transcribed in S phase suppressing chromosome fragility at the M-G1 transition. We propose that an Hmo1-dependent epigenetic signature together with Top2 mediate an S phase architectural pathway to preserve genome integrity.
authors.affiliation: Fondazione IFOM Istituto FIRC di Oncologia Moleculare (IFOM-IEO Campus), Via Adamello 16, 20139 Milan, Italy.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bermejo
authors.forename: Thelma
authors.initials: T
authors.lastname: Capra
authors.forename: Victor
authors.initials: V
authors.lastname: Gonzalez-Huici
authors.forename: Daniele
authors.initials: D
authors.lastname: Fachinetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Cocito
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Natoli
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katou
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
authors.forename: Ken
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Marco
authors.initials: M
authors.lastname: Foiani
mesh_terms: D002873:Chromosome Fragility; D004261:DNA Replication; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D044127:Epigenesis, Genetic; D016681:Genome, Fungal; D006609:High Mobility Group Proteins / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C103154:HMO1 protein, S cerevisiae; D006609:High Mobility Group Proteins; D029701:Saccharomyces cerevisiae Proteins; D012319:RNA Polymerase II; D004250:DNA Topoisomerases, Type II