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Statements

Subject Item
n2:RIV%2F61989592%3A15110%2F10%3A10213205%21RIV13-MSM-15110___
rdf:type
skos:Concept n13:Vysledek
dcterms:description
In response to ionizing radiation (IR), cells delay cell cycle progression and activate DNA repair. Both processes are vital for genome integrity, but the mechanisms involved in their coordination are not fully understood. In a mass spectrometry screen, we identified the adenosine triphosphate-dependent chromatin-remodeling protein CHD4 (chromodomain helicase DNA-binding protein 4) as a factor that becomes transiently immobilized on chromatin after IR. Knockdown of CHD4 triggers enhanced Cdc25A degradation and p21(Cip1) accumulation, which lead to more pronounced cyclin-dependent kinase inhibition and extended cell cycle delay. At DNA double-strand breaks, depletion of CHD4 disrupts the chromatin response at the level of the RNF168 ubiquitin ligase, which in turn impairs local ubiquitylation and BRCA1 assembly. These cell cycle and chromatin defects are accompanied by elevated spontaneous and IR-induced DNA breakage, reduced efficiency of DNA repair, and decreased clonogenic survival. In response to ionizing radiation (IR), cells delay cell cycle progression and activate DNA repair. Both processes are vital for genome integrity, but the mechanisms involved in their coordination are not fully understood. In a mass spectrometry screen, we identified the adenosine triphosphate-dependent chromatin-remodeling protein CHD4 (chromodomain helicase DNA-binding protein 4) as a factor that becomes transiently immobilized on chromatin after IR. Knockdown of CHD4 triggers enhanced Cdc25A degradation and p21(Cip1) accumulation, which lead to more pronounced cyclin-dependent kinase inhibition and extended cell cycle delay. At DNA double-strand breaks, depletion of CHD4 disrupts the chromatin response at the level of the RNF168 ubiquitin ligase, which in turn impairs local ubiquitylation and BRCA1 assembly. These cell cycle and chromatin defects are accompanied by elevated spontaneous and IR-induced DNA breakage, reduced efficiency of DNA repair, and decreased clonogenic survival.
dcterms:title
The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage
skos:prefLabel
The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage
skos:notation
RIV/61989592:15110/10:10213205!RIV13-MSM-15110___
n3:aktivita
n19:Z
n3:aktivity
Z(MSM6198959216)
n3:cisloPeriodika
5
n3:dodaniDat
n14:2013
n3:domaciTvurceVysledku
n16:6201822
n3:druhVysledku
n10:J
n3:duvernostUdaju
n17:S
n3:entitaPredkladatele
n4:predkladatel
n3:idSjednocenehoVysledku
250702
n3:idVysledku
RIV/61989592:15110/10:10213205
n3:jazykVysledku
n11:eng
n3:klicovaSlova
DESTRUCTION; CHROMOSOMES; MDC1; CANCER; CHECKPOINT; S-PHASE; NURD COMPLEX; IONIZING-RADIATION; HISTONE DEACETYLASE; DOUBLE-STRAND BREAKS
n3:klicoveSlovo
n8:CHROMOSOMES n8:IONIZING-RADIATION n8:CANCER n8:NURD%20COMPLEX n8:HISTONE%20DEACETYLASE n8:CHECKPOINT n8:S-PHASE n8:DOUBLE-STRAND%20BREAKS n8:DESTRUCTION n8:MDC1
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[9FAFA1F3B31A]
n3:nazevZdroje
Journal of Cell Biology
n3:obor
n12:EB
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
14
n3:rokUplatneniVysledku
n14:2010
n3:svazekPeriodika
190
n3:tvurceVysledku
Gudjonsson, Thorkell Stucki, Manuel Larsen, Dorthe Poinsignon, Catherine Danielsen, Jannie Andersen, Jens Sand, Jette Lukáš, Jiří Payne, Mark Hari, Flurina Lukas, Claudia Dinant, Christoffel Menard, Patrice Bártek, Jiří
n3:wos
000281781300005
n3:zamer
n18:MSM6198959216
s:issn
0021-9525
s:numberOfPages
9
n5:doi
10.1083/jcb.200912135
n15:organizacniJednotka
15110