title: Defective histone supply causes condensin-dependent chromatin alterations, SAC activation and chromosome decatenation impairment.
abstract: The structural organization of chromosomes is essential for their correct function and dynamics during the cell cycle. The assembly of DNA into chromatin provides the substrate for topoisomerases and condensins, which introduce the different levels of superhelical torsion required for DNA metabolism. In particular, Top2 and condensin are directly involved in both the resolution of precatenanes that form during replication and the formation of the intramolecular loop that detects tension at the centromeric chromatin during chromosome biorientation. Here we show that histone depletion activates the spindle assembly checkpoint (SAC) and impairs sister chromatid decatenation, leading to chromosome mis-segregation and lethality in the absence of the SAC. We demonstrate that histone depletion impairs chromosome biorientation and activates the Aurora-dependent pathway, which detects tension problems at the kinetochore. Interestingly, SAC activation is suppressed by the absence of Top2 and Smc2, an essential component of condensin. Indeed, smc2-8 suppresses catenanes accumulation, mitotic arrest and growth defects induced by histone depletion at semi-permissive temperature. Remarkably, SAC activation by histone depletion is associated with condensin-mediated alterations of the centromeric chromatin. Therefore, our results reveal the importance of a precise interplay between histone supply and condensin/Top2 for pericentric chromatin structure, precatenanes resolution and centromere biorientation.
authors.affiliation: Departamento de Biología Molecular, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Murillo-Pineda
authors.affiliation: Departamento de Biología Molecular, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Cabello-Lobato
authors.affiliation: Departamento de Biología Molecular, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Clemente-Ruiz
authors.affiliation: Universidad de Sevilla (US), Seville, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Monje-Casas
authors.affiliation: Departamento de Biología Molecular, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain felix.prado@cabimer.es.
authors.forename: Félix
authors.initials: F
authors.lastname: Prado
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D064127:Aurora Kinases / Q000502:physiology; D002503:Centromere / Q000502:physiology; D002843:Chromatin / Q000737:chemistry*; D020090:Chromosome Segregation; D015825:Chromosomes, Fungal / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006657:Histones / Q000502:physiology*; D059566:M Phase Cell Cycle Checkpoints; D008677:Metaphase; D046912:Multiprotein Complexes / Q000502:physiology*; D009707:Nucleosomes / Q000502:physiology; D059807:S Phase Cell Cycle Checkpoints; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; C108312:condensin complexes; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; D004250:DNA Topoisomerases, Type II