Ligase 3-mediated end-joining maintains genome stability of human embryonic stem cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F19%3A00108021" target="_blank" >RIV/00216224:14110/19:00108021 - isvavai.cz</a>
Alternative codes found
RIV/00159816:_____/19:00071022
Result on the web
<a href="http://dx.doi.org/10.1096/fj.201801877RR" target="_blank" >http://dx.doi.org/10.1096/fj.201801877RR</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1096/fj.201801877RR" target="_blank" >10.1096/fj.201801877RR</a>
Alternative languages
Result language
angličtina
Original language name
Ligase 3-mediated end-joining maintains genome stability of human embryonic stem cells
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Faseb Journal
ISSN
0892-6638
e-ISSN
1530-6860
Volume of the periodical
33
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
6778-6788
UT code for WoS article
000476114200009
EID of the result in the Scopus database
2-s2.0-85067276713