About: HCLK2 Is Required for Activity of the DNA Damage Response Kinase ATR

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About: HCLK2 Is Required for Activity of the DNA Damage Response Kinase ATR Goto Sponge NotDistinct Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	ATR is a protein kinase that orchestrates the cellular response to replication problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and Chk1. Here we provide evidence that human HCLK2 acts at an early step in the ATR signaling pathway and contributes to full-scale activation of ATR kinase activity.Weshow that HCLK2 forms a complex with ATR-ATRIP and the ATR activator TopBP1. We demonstrate that HCLK2-induced ATR kinase activity toward substrates requires TopBP1 and vice versa and provides evidence that HCLK2 facilitates efficient ATR-TopBP1 association. Consistent with its role in ATR activation, HCLK2 depletion severely impaired phosphorylation of multiple ATR targets including Chk1, Nbs1, and Smc1 after DNA damage. We show that HCLK2 is required for and stimulates ATR autophosphorylation and activity toward different substrates in vitro. Furthermore, HCLK2 depletion abrogated the G2 checkpoint and decreased survival of cells after exposure to DNA damaging agents and replicati ATR is a protein kinase that orchestrates the cellular response to replication problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and Chk1. Here we provide evidence that human HCLK2 acts at an early step in the ATR signaling pathway and contributes to full-scale activation of ATR kinase activity.Weshow that HCLK2 forms a complex with ATR-ATRIP and the ATR activator TopBP1. We demonstrate that HCLK2-induced ATR kinase activity toward substrates requires TopBP1 and vice versa and provides evidence that HCLK2 facilitates efficient ATR-TopBP1 association. Consistent with its role in ATR activation, HCLK2 depletion severely impaired phosphorylation of multiple ATR targets including Chk1, Nbs1, and Smc1 after DNA damage. We show that HCLK2 is required for and stimulates ATR autophosphorylation and activity toward different substrates in vitro. Furthermore, HCLK2 depletion abrogated the G2 checkpoint and decreased survival of cells after exposure to DNA damaging agents and replicati (en)
Title	HCLK2 Is Required for Activity of the DNA Damage Response Kinase ATR HCLK2 Is Required for Activity of the DNA Damage Response Kinase ATR (en)
skos:prefLabel	HCLK2 Is Required for Activity of the DNA Damage Response Kinase ATR HCLK2 Is Required for Activity of the DNA Damage Response Kinase ATR (en)
skos:notation	RIV/61989592:15110/08:00010974!RIV10-MSM-15110___
http://linked.open...avai/riv/aktivita	Z
http://linked.open...avai/riv/aktivity	Z(MSM6198959216)
http://linked.open...iv/cisloPeriodika	284
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	369858
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/08:00010974
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	ATR; DNA damage; replicative stress; checkpoint signaling (en)
http://linked.open.../riv/klicoveSlovo	DNA damage ATR checkpoint signaling replicative stress
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[267FF4CB8E1B]
http://linked.open...i/riv/nazevZdroje	Journal of Biological Chemistry
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	1 (xsd:int)
http://linked.open...cetTvurcuVysledku	7 (xsd:int)
http://linked.open...UplatneniVysledku	2008
http://linked.open...v/svazekPeriodika	13
http://linked.open...iv/tvurceVysledku	Bártek, Jiří Lukas, Jiří Rendtlew Danielsen, Jannie M. Bødtker Schou, Kenneth Falck, Jacob Freire, Raimundo Larsen, Dorthe Helena
http://linked.open...n/vavai/riv/zamer	Modulation of signalling and regulatory pathways in normal and cancer cells
issn	0021-9258
number of pages	8 (xsd:int)
http://localhost/t...ganizacniJednotka	15110

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