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Statements

Subject Item
n2:RIV%2F00216224%3A14110%2F10%3A00067228%21RIV14-MSM-14110___
rdf:type
n14:Vysledek skos:Concept
dcterms:description
Embryonic stem cells progress very rapidly through the cell cycle, allowing limited time for cell cycle regulatory circuits that typically function in somatic cells. Mechanisms that inhibit cell cycle progression upon DNA damage are of particular importance, as their malfunction may contribute to the genetic instability observed in human embryonic stem cells (hESCs). In this study, we exposed undifferentiated hESCs to DNA-damaging ultraviolet radiation-C range (UVC) light and examined their progression through the G1/S transition. We show that hESCs irradiated in G1 phase undergo cell cycle arrest before DNA synthesis and exhibit decreased cyclin-dependent kinase two (CDK2) activity. We also show that the phosphatase Cdc25A, which directly activates CDK2, is downregulated in irradiated hESCs through the action of the checkpoint kinases Chk1 and/or Chk2. Importantly, the classical effector of the p53-mediated pathway, protein p21, is not a regulator of G1/S progression in hESCs. Embryonic stem cells progress very rapidly through the cell cycle, allowing limited time for cell cycle regulatory circuits that typically function in somatic cells. Mechanisms that inhibit cell cycle progression upon DNA damage are of particular importance, as their malfunction may contribute to the genetic instability observed in human embryonic stem cells (hESCs). In this study, we exposed undifferentiated hESCs to DNA-damaging ultraviolet radiation-C range (UVC) light and examined their progression through the G1/S transition. We show that hESCs irradiated in G1 phase undergo cell cycle arrest before DNA synthesis and exhibit decreased cyclin-dependent kinase two (CDK2) activity. We also show that the phosphatase Cdc25A, which directly activates CDK2, is downregulated in irradiated hESCs through the action of the checkpoint kinases Chk1 and/or Chk2. Importantly, the classical effector of the p53-mediated pathway, protein p21, is not a regulator of G1/S progression in hESCs.
dcterms:title
Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation
skos:prefLabel
Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation Human Embryonic Stem Cells Are Capable of Executing G1/S Checkpoint Activation
skos:notation
RIV/00216224:14110/10:00067228!RIV14-MSM-14110___
n3:aktivita
n9:S n9:P n9:Z
n3:aktivity
P(NS10439), S, Z(AV0Z50390512), Z(AV0Z50390703), Z(MSM0021622430)
n3:cisloPeriodika
7
n3:dodaniDat
n18:2014
n3:domaciTvurceVysledku
n4:1957864 n4:3015459 n4:9569707 n4:9400753 n4:8064296 n4:5709164 n4:7935064 n4:1721933
n3:druhVysledku
n5:J
n3:duvernostUdaju
n19:S
n3:entitaPredkladatele
n12:predkladatel
n3:idSjednocenehoVysledku
262331
n3:idVysledku
RIV/00216224:14110/10:00067228
n3:jazykVysledku
n13:eng
n3:klicovaSlova
Human embryonic stem cells; DNA damage; Checkpoint activation; UVC; Cdc25A; p53
n3:klicoveSlovo
n7:Human%20embryonic%20stem%20cells n7:Cdc25A n7:Checkpoint%20activation n7:p53 n7:UVC n7:DNA%20damage
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[0CF2204445E1]
n3:nazevZdroje
Stem Cells
n3:obor
n15:EB
n3:pocetDomacichTvurcuVysledku
8
n3:pocetTvurcuVysledku
8
n3:projekt
n20:NS10439
n3:rokUplatneniVysledku
n18:2010
n3:svazekPeriodika
28
n3:tvurceVysledku
Verner, Jan Pospíšilová, Šárka Bárta, Tomáš Dvořák, Petr Vinarský, Vladimír Doležalová, Dáša Hampl, Aleš Holubcová, Zuzana
n3:wos
000280746400004
n3:zamer
n16:MSM0021622430 n16:AV0Z50390703 n16:AV0Z50390512
s:issn
1066-5099
s:numberOfPages
10
n11:doi
10.1002/stem.451
n17:organizacniJednotka
14110