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...
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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.