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.

Friedrich Miescher Institute for Biomedical Research Maulbeerstr 66 CH 4058 Basel Switzerland

Graduate School of Chemistry Westfälische Wilhelms Universität D 48149 Münster Germany

Institut for Biochemistry Westfälische Wilhelms Universität D 48149 Münster Germany

Institute of Molecular Cancer Research University of Zurich Winterthurerstr 190 CH 8057 Zürich Switzerland

Institute of Molecular Genetics Academy of Sciences of the Czech Republic 143 00 Prague Czech Republic

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