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@article{1603917,
author = {Kohutová, Aneta and Raška, Jan and Krutá, Miriama and Šeneklová, Monika and Bárta, Tomáš and Fojtík, Petr and Juráková, Tereza and Walter, Christi A. and Hampl, Aleš and Dvořák, Petr and Rotrekl, Vladimír},
article_location = {BETHESDA},
article_number = {6},
doi = {http://dx.doi.org/10.1096/fj.201801877RR},
keywords = {base excision repair; PARP1; 53BP1; pluripotent stem cells; alternative DNA end-joining},
language = {eng},
issn = {0892-6638},
journal = {Faseb Journal},
title = {Ligase 3-mediated end-joining maintains genome stability of human embryonic stem cells},
url = {http://dx.doi.org/10.1096/fj.201801877RR},
volume = {33},
year = {2019}
}
TY - JOUR
ID - 1603917
AU - Kohutová, Aneta - Raška, Jan - Krutá, Miriama - Šeneklová, Monika - Bárta, Tomáš - Fojtík, Petr - Juráková, Tereza - Walter, Christi A. - Hampl, Aleš - Dvořák, Petr - Rotrekl, Vladimír
PY - 2019
TI - Ligase 3-mediated end-joining maintains genome stability of human embryonic stem cells
JF - Faseb Journal
VL - 33
IS - 6
SP - 6778-6788
EP - 6778-6788
PB - FEDERATION AMER SOC EXP BIOL
SN - 08926638
KW - base excision repair
KW - PARP1
KW - 53BP1
KW - pluripotent stem cells
KW - alternative DNA end-joining
UR - http://dx.doi.org/10.1096/fj.201801877RR
L2 - http://dx.doi.org/10.1096/fj.201801877RR
N2 - Maintenance of human embryonic stem cells (hESCs) with stable genome is important for their future use in cell replacement therapy and disease modeling. Our understanding of the mechanisms maintaining genomic stability of hESC and our ability to modulate them is essential in preventing unwanted mutation accumulation during their in vitro cultivation. In this study, we show the DNA damage response mechanism in hESCs is composed of known, yet unlikely components. Clustered oxidative base damage is converted into DNA double-strand breaks (DSBs) by base excision repair (BER) and then quickly repaired by ligase (Lig)3-mediated end-joining (EJ). If there is further induction of clustered oxidative base damage by irradiation, then BER-mediated DSBs become essential in triggering the checkpoint response in hESCs. hESCs limit the mutagenic potential of Lig3-mediated EJ by DNA break end protection involving p53 binding protein 1 (53BP1), which results in fast and error-free microhomology-mediated repair and a low mutant frequency in hESCs. DSBs in hESCs are also repaired via homologous recombination (HR); however, DSB overload, together with massive end protection by 53BP1, triggers competition between error-free HR and mutagenic nonhomologous EJ.-Kohutova, A., Raska, J., Kruta, M., Seneklova, M., Barta, T., Fojtik, P., Jurakova, T., Walter, C. A., Hampl, A., Dvorak, P., Rotrekl, V. Ligase 3-mediated end-joining maintains genome stability of human embryonic stem cells.
ER -
KOHUTOVÁ, Aneta, Jan RAŠKA, Miriama KRUTÁ, Monika ŠENEKLOVÁ, Tomáš BÁRTA, Petr FOJTÍK, Tereza JURÁKOVÁ, Christi A. WALTER, Aleš HAMPL, Petr DVOŘÁK and Vladimír ROTREKL. Ligase 3-mediated end-joining maintains genome stability of human embryonic stem cells. \textit{Faseb Journal}. BETHESDA: FEDERATION AMER SOC EXP BIOL, 2019, vol.~33, No~6, p.~6778-6788. ISSN~0892-6638. Available from: https://dx.doi.org/10.1096/fj.201801877RR.
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