title: Human SIRT1 associates with mitotic chromatin and contributes to chromosomal condensation.
abstract: SIRT1 is a NAD-dependent deacetylase that participates in cellular controls of gene expression, metabolism, genomic stability and anti-aging. Here we report that SIRT1 levels rise in prometaphase leading to SIRT1 global association with mitotic chromatin until telophase. Moreover, SIRT1 contributes to chromosomal condensation by mediating chromosomal loading of histone H1 and the condensin I complex. Consistently, SIRT1 knockdown led to improper condensation and overall aberrant mitosis. Our data highlight new role for SIRT1 in maintenance of chromosome stability in mitosis and suggests how diminished SIRT1 activity during aging and tumorigenesis may lead to aneuploidy and genomic instability.
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London, UK.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Fatoba
authors.forename: Andrei L
authors.initials: AL
authors.lastname: Okorokov
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000782:Aneuploidy; D000818:Animals; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D002843:Chromatin / Q000378:metabolism*; D043171:Chromosomal Instability; D002877:Chromosomes, Human / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008938:Mitosis; D046912:Multiprotein Complexes / Q000378:metabolism; D049468:Prometaphase; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D013692:Telophase
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; C108312:condensin complexes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000251:Adenosine Triphosphatases