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Description
| - Naše výsledky ukazují, že akumulace fosphorylovaného Chk1 na centrosomech vytváří přídavný element v odpovědi na poškození DNA (DDR). Centrosomální Chk1 indukuje zastavení buněčného cyklu v G/M bodě a může evokovat centrosomální amplifikaci. (cs)
- The checkpoint kinase Chk1 is an established transducer of ATR- and ATM-dependent signalling in response to DNA damage. In addition to its nuclear localization, Chk1 localizes to interphase centrosomes and thereby negatively regulates entry into mitosis by preventing premature activation of cyclin B-Cdk1 during unperturbed cell cycles. Here, we demonstrate that DNA damage caused by ultraviolet irradiation or hydroxyurea treatment leads to centrosomal accumulation of endogenous Chk1 in normal human BJ fibroblasts and in ATR- or ATM-deficient fibroblasts. Chemical inhibition of ATR/ATM by caffeine led to enhanced centrosomal Chk1 deposition associated with nuclear Chk1 depletion. In contrast to normal or ATM-deficient fibroblasts, genetically ATR-deficient Seckel-fibroblasts showed detectable constitutive centrosomal accumulation of Chk1 even in the absence of exogenous insults. After DNA damage, the centrosomal fraction of Chk1 was found to be phosphorylated at ATR/ATM phosphorylation sites. Forced imm
- The checkpoint kinase Chk1 is an established transducer of ATR- and ATM-dependent signalling in response to DNA damage. In addition to its nuclear localization, Chk1 localizes to interphase centrosomes and thereby negatively regulates entry into mitosis by preventing premature activation of cyclin B-Cdk1 during unperturbed cell cycles. Here, we demonstrate that DNA damage caused by ultraviolet irradiation or hydroxyurea treatment leads to centrosomal accumulation of endogenous Chk1 in normal human BJ fibroblasts and in ATR- or ATM-deficient fibroblasts. Chemical inhibition of ATR/ATM by caffeine led to enhanced centrosomal Chk1 deposition associated with nuclear Chk1 depletion. In contrast to normal or ATM-deficient fibroblasts, genetically ATR-deficient Seckel-fibroblasts showed detectable constitutive centrosomal accumulation of Chk1 even in the absence of exogenous insults. After DNA damage, the centrosomal fraction of Chk1 was found to be phosphorylated at ATR/ATM phosphorylation sites. Forced imm (en)
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Title
| - DNA damage-induced accumulation of centrosomal Chk1 contributes to its checkpoint function
- DNA damage-induced accumulation of centrosomal Chk1 contributes to its checkpoint function (en)
- Poškození DNA - indukovaná akumulace centrosomální kinasy Chk1 přispívá k její roli kontrolního bodu (cs)
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skos:prefLabel
| - DNA damage-induced accumulation of centrosomal Chk1 contributes to its checkpoint function
- DNA damage-induced accumulation of centrosomal Chk1 contributes to its checkpoint function (en)
- Poškození DNA - indukovaná akumulace centrosomální kinasy Chk1 přispívá k její roli kontrolního bodu (cs)
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skos:notation
| - RIV/61989592:15310/07:00004909!RIV08-MSM-15310___
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http://linked.open.../vavai/riv/strany
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/61989592:15310/07:00004909
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - Cell Line, Tumor; Centrosome/metabolism; DNA Damage/*genetics; G2 Phase; Gene Amplification/genetics; Humans; Mutation/genetics; Phosphorylation; Protein Kinases/*metabolism (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Bártek, Jiří
- Krämer, Alwin
- Lukáš, Jiří
- Tews, Björn
- Löffler, Harald
- Ho, Anthony D.
- Bochtler, Tilmann
- Fritz, Britta
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http://linked.open...n/vavai/riv/zamer
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issn
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number of pages
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http://localhost/t...ganizacniJednotka
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