Ligase 3-mediated end-joining maintains genome stability of
human embryonic stem cells

J 2019

Ligase 3-mediated end-joining maintains genome stability of human embryonic stem cells

KOHUTOVÁ, Aneta, Jan RAŠKA, Miriama KRUTÁ, Monika ŠENEKLOVÁ, Tomáš BÁRTA et. al.

Basic information

Original name

Ligase 3-mediated end-joining maintains genome stability of human embryonic stem cells

Authors

KOHUTOVÁ, Aneta (703 Slovakia, belonging to the institution), Jan RAŠKA (203 Czech Republic, belonging to the institution), Miriama KRUTÁ (703 Slovakia, belonging to the institution), Monika ŠENEKLOVÁ (203 Czech Republic, belonging to the institution), Tomáš BÁRTA (203 Czech Republic, belonging to the institution), Petr FOJTÍK (203 Czech Republic, belonging to the institution), Tereza JURÁKOVÁ (203 Czech Republic, belonging to the institution), Christi A. WALTER (840 United States of America), Aleš HAMPL (203 Czech Republic, belonging to the institution), Petr DVOŘÁK (203 Czech Republic, belonging to the institution) and Vladimír ROTREKL (203 Czech Republic, guarantor, belonging to the institution)

Edition

Faseb Journal, BETHESDA, FEDERATION AMER SOC EXP BIOL, 2019, 0892-6638

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.966

RIV identification code

RIV/00216224:14110/19:00108021

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1096/fj.201801877RR

UT WoS

000476114200009

Keywords in English

base excision repair; PARP1; 53BP1; pluripotent stem cells; alternative DNA end-joining

Abstract

V originále

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.

Links

GBP302/12/G157, research and development project

Name: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

Investor: Czech Science Foundation

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1087/2018, interní kód MU

Name: Molekulární a buněčná biologie pro biomedicínské vědy

Investor: Masaryk University, Category A

MUNI/C/0967/2013, interní kód MU

Name: Role homologní rekombinace v údržbě genomové stability u dlouhodobě kultivovaných lidských pluripotentních buněk

Investor: Masaryk University, Rector's Program

Citovat

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. 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.

@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.

Detailed Information on Publication Record