Institut for Biochemistry, Westfälische-Wilhelms-Universität, D-48149 Münster, Germany.
Graduate School of Chemistry (GSC-MS), Westfälische-Wilhelms-Universität, D-48149 Münster, Germany.
Sci Rep. 2017 Jan 27;7:41663. doi: 10.1038/srep41663.
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.
B-Myb 是 Myb 转录因子家族中的一个高度保守成员，在增殖细胞中广泛表达，控制 G2/M 期基因的细胞周期依赖性转录。B-Myb 的失调与肿瘤发生和基因组稳定性丧失有关。我们已经确定 B-Myb 是 Mre11-Rad50-Nbs1（MRN）复合物的一个新的相互作用伙伴，MRN 复合物是 DNA 双链断裂修复的关键参与者。我们表明，B-Myb 直接与 MRN 复合物的 Nbs1 亚基相互作用，并被短暂招募到 DNA 损伤部位。在 DNA 损伤反应中，B-Myb 被蛋白激酶 GSK3β磷酸化，并从 MRN 复合物中释放出来。一种不能被 GSK3β 磷酸化的 B-Myb 突变体扰乱了促有丝分裂 B-Myb 靶基因的调节，导致在 DNA 损伤时不适当的有丝分裂进入。总的来说，我们的工作表明 B-Myb 在细胞 DNA 损伤信号转导中具有新的功能。
