Počet záznamů: 1
Decrease in Abundance of Apurinic/Apyrimidinic Endonuclease Causes Failure of Base Excision Repair in Culture-Adapted Human Embryonic Stem Cells
- 1.0392615 - BFÚ 2014 RIV US eng J - Článek v odborném periodiku
Krutá, M. - Bálek, L. - Hejnová, R. - Dobšáková, Z. - Eiselleová, L. - Matulka, K. - Bárta, T. - Fojtík, P. - Fajkus, Jiří - Hampl, A. - Dvořák, P. - Rotrekl, V.
Decrease in Abundance of Apurinic/Apyrimidinic Endonuclease Causes Failure of Base Excision Repair in Culture-Adapted Human Embryonic Stem Cells.
Stem Cells. Roč. 31, č. 4 (2013), s. 693-702. ISSN 1066-5099. E-ISSN 1549-4918
Grant CEP: GA ČR(CZ) GBP302/12/G157
Grant ostatní: GA MŠk(CZ) ED1.100/02/0123
Institucionální podpora: RVO:68081707
Klíčová slova: DNA-DAMAGE * GENOMIC INSTABILITY * HETEROZYGOUS MICE
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 7.133, rok: 2013
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 link between BER and double-strand breaks (DSB) was demonstrated by decreased DSB release after downregulation of APE1 in early passage hESCs via siRNA. Correspondingly lower APE1 level in late passage hESC resulted in slower and less intensive but long lasting DSB release upon ionizing radiation (IR).
Trvalý link: http://hdl.handle.net/11104/0221439
Počet záznamů: 1