title: Repo-Man coordinates chromosomal reorganization with nuclear envelope reassembly during mitotic exit.
abstract: Repo-Man targets protein phosphatase 1 γ (PP1γ) to chromatin at anaphase onset and regulates chromosome structure during mitotic exit. Here, we show that a Repo-Man:PP1 complex forms in anaphase following dephosphorylation of Repo-Man. Upon activation, the complex localizes to chromosomes and causes the dephosphorylation of histone H3 (Thr3, Ser10, and Ser28). In anaphase, Repo-Man has both catalytic and structural functions that are mediated by two separate domains. A C-terminal domain localizes Repo-Man to bulk chromatin in early anaphase. There, it targets PP1 for the dephosphorylation of histone H3 and possibly other chromosomal substrates. An N-terminal domain localizes Repo-Man to the chromosome periphery later in anaphase. There, it is responsible for the recruitment of nuclear components such as Importin β and Nup153 in a PP1-independent manner. These observations identify Repo-Man as a key factor that coordinates chromatin remodeling and early events of nuclear envelope reformation during mitotic exit.
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK. p.vagnarelli@ed.ac.uk
authors.forename: Paola
authors.initials: P
authors.lastname: Vagnarelli
authors.forename: Susana
authors.initials: S
authors.lastname: Ribeiro
authors.forename: Lau
authors.initials: L
authors.lastname: Sennels
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Pulido
authors.forename: Flavia
authors.initials: F
authors.lastname: de Lima Alves
authors.forename: Toon
authors.initials: T
authors.lastname: Verheyen
authors.forename: David A
authors.initials: DA
authors.lastname: Kelly
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: William C
authors.initials: WC
authors.lastname: Earnshaw
mesh_terms: D000705:Anaphase / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D002875:Chromosomes / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009685:Nuclear Envelope / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods; D014162:Transfection; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: C509224:CDCA2 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D006657:Histones; D009687:Nuclear Proteins; D017476:Receptors, Neuropeptide Y; D028961:beta Karyopherins; D049452:Green Fluorescent Proteins; C109491:neuropeptide Y4 receptor