Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage modified chromatin

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F08%3A00009721" target="_blank" >RIV/61989592:15110/08:00009721 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage modified chromatin

Popis výsledku v původním jazyce

DNA double-strand breaks (DSBs) trigger accumulation of the MRE11 - RAD50- Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on the DSB-fl anking chromatin facilitates survival. Chromatin retention of MRN requires the MDC1 adaptor protein, but the mechanism behind the MRN - MDC1 interaction is unknown. We show that the NBS1 subunit of MRN interacts with the MDC1 N terminus enriched in Ser-Asp- Thr (SDT) repeats. This interaction was constitutive and mediated by binding between the phosphorylated SDT repeats of MDC1 and the phosphate-binding forkhead-associated domain of NBS1. Phosphorylation of the SDT repeats by casein kinase 2 (CK2) was suffi cient to trigger MDC1- NBS1 interaction in vitro, and MDC1 associated with CK2 activity in cells. Inhibition of CK2 reduced SDT phosphorylation in vivo, and disruption of the SDT-associated phosphoacceptor sites prevented the retention of NBS1 at DSBs. Together, these data suggest that phosphorylation of the SDT repeats in the M

Název v anglickém jazyce

Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage modified chromatin

Popis výsledku anglicky

DNA double-strand breaks (DSBs) trigger accumulation of the MRE11 - RAD50- Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on the DSB-fl anking chromatin facilitates survival. Chromatin retention of MRN requires the MDC1 adaptor protein, but the mechanism behind the MRN - MDC1 interaction is unknown. We show that the NBS1 subunit of MRN interacts with the MDC1 N terminus enriched in Ser-Asp- Thr (SDT) repeats. This interaction was constitutive and mediated by binding between the phosphorylated SDT repeats of MDC1 and the phosphate-binding forkhead-associated domain of NBS1. Phosphorylation of the SDT repeats by casein kinase 2 (CK2) was suffi cient to trigger MDC1- NBS1 interaction in vitro, and MDC1 associated with CK2 activity in cells. Inhibition of CK2 reduced SDT phosphorylation in vivo, and disruption of the SDT-associated phosphoacceptor sites prevented the retention of NBS1 at DSBs. Together, these data suggest that phosphorylation of the SDT repeats in the M

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

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Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2008

Kód důvěrnosti údajů

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

Název periodika

Journal of Cell Biology

ISSN

0021-9525

e-ISSN

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Svazek periodika

181

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

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Kód UT WoS článku

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EID výsledku v databázi Scopus

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