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Statements

Subject Item
n2:RIV%2F00216224%3A14110%2F13%3A00065577%21RIV14-MZ0-14110___
rdf:type
skos:Concept n12:Vysledek
dcterms:description
The inevitable accumulation of chromosomal abnormalities in human embryonic stem cells (hESCs) during in vitro expansion represents a considerable obstacle for cell replacement therapies. To determine the source of chromosomal abnormalities, we examined hESCs maintained in culture for over 55 months for defects in telomere maintenance and DNA repair. Although prolonged culture affected neither telomerase activity nor nonhomologous end joining, the efficiency of base excision repair (BER) was significantly decreased and correlated with reduced expression of apurinic/apyrimidinic endonuclease 1 (APE1), the major nuclease required for BER. Interestingly, the expression of other BER enzymes was unchanged. Addition of human recombinant APE1 protein to nuclear extracts from late passage hESCs increased BER efficiency to the level typical of early passage hESCs. The inevitable accumulation of chromosomal abnormalities in human embryonic stem cells (hESCs) during in vitro expansion represents a considerable obstacle for cell replacement therapies. To determine the source of chromosomal abnormalities, we examined hESCs maintained in culture for over 55 months for defects in telomere maintenance and DNA repair. Although prolonged culture affected neither telomerase activity nor nonhomologous end joining, the efficiency of base excision repair (BER) was significantly decreased and correlated with reduced expression of apurinic/apyrimidinic endonuclease 1 (APE1), the major nuclease required for BER. Interestingly, the expression of other BER enzymes was unchanged. Addition of human recombinant APE1 protein to nuclear extracts from late passage hESCs increased BER efficiency to the level typical of early passage hESCs.
dcterms:title
Decrease in Abundance of apurinic/apyrimidinic Endonuclease Causes Failure of Base Excision Repair in Culture-Adapted Human Embryonic Stem Cells Decrease in Abundance of apurinic/apyrimidinic Endonuclease Causes Failure of Base Excision Repair in Culture-Adapted Human Embryonic Stem Cells
skos:prefLabel
Decrease in Abundance of apurinic/apyrimidinic Endonuclease Causes Failure of Base Excision Repair in Culture-Adapted Human Embryonic Stem Cells Decrease in Abundance of apurinic/apyrimidinic Endonuclease Causes Failure of Base Excision Repair in Culture-Adapted Human Embryonic Stem Cells
skos:notation
RIV/00216224:14110/13:00065577!RIV14-MZ0-14110___
n12:predkladatel
n15:orjk%3A14110
n3:aktivita
n5:P n5:I
n3:aktivity
I, P(GBP302/12/G157), P(NS10237)
n3:cisloPeriodika
4
n3:dodaniDat
n13:2014
n3:domaciTvurceVysledku
n8:9569707 n8:8202575 n8:3557685 n8:5709164 n8:8064296 n8:9659927 n8:6048838 n8:9120548 n8:7586132 n8:5655064 n8:8422176 n8:4887190
n3:druhVysledku
n20:J
n3:duvernostUdaju
n18:S
n3:entitaPredkladatele
n9:predkladatel
n3:idSjednocenehoVysledku
68112
n3:idVysledku
RIV/00216224:14110/13:00065577
n3:jazykVysledku
n14:eng
n3:klicovaSlova
APE1; base excision repair; human embryonic stem cells; culture adaptation; genome instability
n3:klicoveSlovo
n7:base%20excision%20repair n7:genome%20instability n7:APE1 n7:human%20embryonic%20stem%20cells n7:culture%20adaptation
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[5AF4ACD1F67F]
n3:nazevZdroje
Stem Cells
n3:obor
n17:EB
n3:pocetDomacichTvurcuVysledku
12
n3:pocetTvurcuVysledku
12
n3:projekt
n4:NS10237 n4:GBP302%2F12%2FG157
n3:rokUplatneniVysledku
n13:2013
n3:svazekPeriodika
31
n3:tvurceVysledku
Hampl, Aleš Bárta, Tomáš Dvořák, Petr Rotrekl, Vladimír Bálek, Lukáš Fajkus, Jiří Fojtík, Petr Krutá, Miriama Matulka, Kamil Hejnová, Renata Eiselleová, Lívia Kunická, Zuzana
n3:wos
000316624300008
s:issn
1066-5099
s:numberOfPages
10
n11:doi
10.1002/stem.1312
n16:organizacniJednotka
14110