Interplay with the Mre11-Rad50-Nbs1 complex and phosphorylation by GSK3 beta implicate human B-Myb in DNA-damage signaling

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F17%3A00507504" target="_blank" >RIV/68378050:_____/17:00507504 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/srep41663" target="_blank" >https://www.nature.com/articles/srep41663</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/srep41663" target="_blank" >10.1038/srep41663</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Interplay with the Mre11-Rad50-Nbs1 complex and phosphorylation by GSK3 beta implicate human B-Myb in DNA-damage signaling

Popis výsledku v původním jazyce

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 GSK3 beta and released from the MRN complex. A B-Myb mutant that cannot be phosphorylated by GSK3 beta 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.

Název v anglickém jazyce

Interplay with the Mre11-Rad50-Nbs1 complex and phosphorylation by GSK3 beta implicate human B-Myb in DNA-damage signaling

Popis výsledku anglicky

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 GSK3 beta and released from the MRN complex. A B-Myb mutant that cannot be phosphorylated by GSK3 beta 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

7

Číslo periodika v rámci svazku

January

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

41663

Kód UT WoS článku

000393020000001

EID výsledku v databázi Scopus

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