title: Histone supply regulates S phase timing and cell cycle progression.
abstract: Eukaryotes package DNA into nucleosomes that contain a core of histone proteins. During DNA replication, nucleosomes are disrupted and re-assembled with newly synthesized histones and DNA. Despite much progress, it is still unclear why higher eukaryotes contain multiple core histone genes, how chromatin assembly is controlled, and how these processes are coordinated with cell cycle progression. We used a histone null mutation of Drosophila melanogaster to show that histone supply levels, provided by a defined number of transgenic histone genes, regulate the length of S phase during the cell cycle. Lack of de novo histone supply not only extends S phase, but also causes a cell cycle arrest during G2 phase, and thus prevents cells from entering mitosis. Our results suggest a novel cell cycle surveillance mechanism that monitors nucleosome assembly without involving the DNA repair pathways and exerts its effect via suppression of CDC25 phosphatase String expression.
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Günesdogan
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Jäckle
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany Abteilung Zelluläre Mikrobiologie, Max-Planck-Institut für Infektionsbiologie, Berlin, Germany herzig@mpiib-berlin.mpg.de.
authors.forename: Alf
authors.initials: A
authors.lastname: Herzig
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D000071877:Checkpoint Kinase 1; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000235:genetics*; D013997:Time Factors; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D006657:Histones; D009707:Nucleosomes; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C444435:Mei-41 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases; C059217:stg protein, Drosophila
keywords: cell cycle control; chromatin assembly; histones