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

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About: Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage modified chromatin Goto Sponge NotDistinct Permalink

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	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 MDC1 N terminus 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 MDC1 N terminus (en)
Title	Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage modified chromatin Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage modified chromatin (en)
skos:prefLabel	Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage modified chromatin Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage modified chromatin (en)
skos:notation	RIV/61989592:15110/08:00009721!RIV10-MSM-15110___
http://linked.open...avai/riv/aktivita	Z
http://linked.open...avai/riv/aktivity	Z(MSM6198959216)
http://linked.open...iv/cisloPeriodika	2
http://linked.open...vai/riv/dodaniDat	2010
http://linked.open...aciTvurceVysledku	Bártek, Jiří
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Lékařská fakulta
http://linked.open...dnocenehoVysledku	386512
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/08:00009721
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	DNA double-strand break; MRN complex; SDT repeats; DNA repair (en)
http://linked.open.../riv/klicoveSlovo	DNA repair DNA double-strand break MRN complex SDT repeats
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[2EC6F8E0A52F]
http://linked.open...i/riv/nazevZdroje	Journal of Cell Biology
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	6 (xsd:int)
http://linked.open...UplatneniVysledku	2008
http://linked.open...v/svazekPeriodika	181
http://linked.open...iv/tvurceVysledku	Bártek, Jiří Bekker-Jensen, Simon Lukas, Jiří Melander ,, Fredrik Falck, Jacob Mailand ,, Niels
http://linked.open...n/vavai/riv/zamer	Modulation of signalling and regulatory pathways in normal and cancer cells
issn	0021-9525
number of pages	14 (xsd:int)
http://localhost/t...ganizacniJednotka	15110

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