title: FACT prevents the accumulation of free histones evicted from transcribed chromatin and a subsequent cell cycle delay in G1.
abstract: The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down-regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3) in START by specifically triggering the repression of its promoter. The G1 delay undergone by spt16 mutants is not mediated by the DNA-damage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197. We reveal how FACT dysfunction triggers an accumulation of free histones evicted from transcribed chromatin. This accumulation is enhanced in a rad53 background and leads to a delay in G1. Consistently, we show that the overexpression of histones in wild-type cells down-regulates CLN3 in START and causes a delay in G1. Our work shows that chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatin and describes a new cell cycle phenomenon that allows cells to respond to excess histones before starting DNA replication.
authors.affiliation: Departamento de Genética, Universidad de Sevilla, Seville, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Morillo-Huesca
authors.forename: Douglas
authors.initials: D
authors.lastname: Maya
authors.forename: Mari Cruz
authors.initials: MC
authors.lastname: Muñoz-Centeno
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Singh
authors.forename: Vincent
authors.initials: V
authors.lastname: Oreal
authors.forename: Gajjalaiahvari Ugander
authors.initials: GU
authors.lastname: Reddy
authors.forename: Dun
authors.initials: D
authors.lastname: Liang
authors.forename: Vincent
authors.initials: V
authors.lastname: Géli
authors.forename: Akash
authors.initials: A
authors.lastname: Gunjan
authors.forename: Sebastián
authors.initials: S
authors.lastname: Chávez
mesh_terms: D015152:Blotting, Northern; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D016193:G1 Phase / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C079895:CLN3 protein, S cerevisiae; D002843:Chromatin; D016213:Cyclins; D004268:DNA-Binding Proteins; C541535:FACT protein, S cerevisiae; D006609:High Mobility Group Proteins; D006657:Histones; D012333:RNA, Messenger; C071238:SPT16 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035602:Transcriptional Elongation Factors