About: Decrease in Abundance of apurinic/apyrimidinic Endonuclease Causes Failure of Base Excision Repair in Culture-Adapted Human Embryonic Stem Cells     Goto   Sponge   NotDistinct   Permalink

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  • 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. (en)
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 (en)
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 (en)
skos:notation
  • RIV/00216224:14110/13:00065577!RIV14-MZ0-14110___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(GBP302/12/G157), P(NS10237)
http://linked.open...iv/cisloPeriodika
  • 4
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...dnocenehoVysledku
  • 68112
http://linked.open...ai/riv/idVysledku
  • RIV/00216224:14110/13:00065577
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • APE1; base excision repair; human embryonic stem cells; culture adaptation; genome instability (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [5AF4ACD1F67F]
http://linked.open...i/riv/nazevZdroje
  • Stem Cells
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 31
http://linked.open...iv/tvurceVysledku
  • Dvořák, Petr
  • Hampl, Aleš
  • Bárta, Tomáš
  • Fajkus, Jiří
  • Fojtík, Petr
  • Bálek, Lukáš
  • Matulka, Kamil
  • Eiselleová, Lívia
  • Hejnová, Renata
  • Krutá, Miriama
  • Kunická, Zuzana
  • Rotrekl, Vladimír
http://linked.open...ain/vavai/riv/wos
  • 000316624300008
issn
  • 1066-5099
number of pages
http://bibframe.org/vocab/doi
  • 10.1002/stem.1312
http://localhost/t...ganizacniJednotka
  • 14110
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