title: Interplay with the Mre11-Rad50-Nbs1 complex and phosphorylation by GSK3β implicate human B-Myb in DNA-damage signaling.
abstract: B-Myb, a highly conserved member of the Myb transcription factor family, is expressed ubiquitously in proliferating cells and controls the cell cycle dependent transcription of G2/M-phase genes. Deregulation of B-Myb has been implicated in oncogenesis and loss of genomic stability. We have identified B-Myb as a novel interaction partner of the Mre11-Rad50-Nbs1 (MRN) complex, a key player in the repair of DNA double strand breaks. We show that B-Myb directly interacts with the Nbs1 subunit of the MRN complex and is recruited transiently to DNA-damage sites. In response to DNA-damage B-Myb is phosphorylated by protein kinase GSK3β and released from the MRN complex. A B-Myb mutant that cannot be phosphorylated by GSK3β disturbs the regulation of pro-mitotic B-Myb target genes and leads to inappropriate mitotic entry in response to DNA-damage. Overall, our work suggests a novel function of B-Myb in the cellular DNA-damage signalling.
authors.affiliation: Institut for Biochemistry, Westfälische-Wilhelms-Universität, D-48149 Münster, Germany.|Graduate School of Chemistry (GSC-MS), Westfälische-Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Sarah Marie
authors.initials: SM
authors.lastname: Henrich
authors.affiliation: Institut for Biochemistry, Westfälische-Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Usadel
authors.affiliation: Institut for Biochemistry, Westfälische-Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Eugen
authors.initials: E
authors.lastname: Werwein
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 143 00 Prague, Czech Republic.
authors.forename: Kamila
authors.initials: K
authors.lastname: Burdova
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 143 00 Prague, Czech Republic.|Institute of Molecular Cancer Research, University of Zurich, Winterthurerstr.190, CH-8057 Zürich, Switzerland.
authors.forename: Pavel
authors.initials: P
authors.lastname: Janscak
authors.affiliation: Institute of Molecular Cancer Research, University of Zurich, Winterthurerstr.190, CH-8057 Zürich, Switzerland.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstr. 66, CH-4058 Basel, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hess
authors.affiliation: Institut for Biochemistry, Westfälische-Wilhelms-Universität, D-48149 Münster, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Klempnauer
mesh_terms: D017766:Acid Anhydride Hydrolases; D000595:Amino Acid Sequence; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D000076228:MRE11 Homologue Protein / Q000737:chemistry / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; D046912:Multiprotein Complexes; C112156:NBN protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D064007:Ataxia Telangiectasia Mutated Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes