Interplay with the Mre11-Rad50-Nbs1 complex and phosphorylation by GSK3β implicate human B-Myb in DNA-damage signaling

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 identifie...

Verfasser: Henrich, Sarah
Usadel, Clemens
Werwein, Eugen
Burdová, Kamila
Janščák, Pavel
Ferrari, Stefano
Hess, Daniel
Klempnauer, Karl-Heinz
Dokumenttypen:Artikel
Medientypen:Text
Erscheinungsdatum:2017
Publikation in MIAMI:23.08.2017
Datum der letzten Änderung:24.06.2021
Angaben zur Ausgabe:[Electronic ed.]
Quelle:Scientific Reports 7 (2017), 41663, 1-14
Fachgebiet (DDC):540: Chemie
Lizenz:CC BY 4.0
Sprache:English
Anmerkungen:Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF-Dokument
ISSN:2045-2322
URN:urn:nbn:de:hbz:6-11239615095
Weitere Identifikatoren:DOI: 10.1038/srep41663
Permalink:https://nbn-resolving.de/urn:nbn:de:hbz:6-11239615095
Onlinezugriff:srep41663.pdf

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.