TREX2 Exonuclease Causes Spontaneous Mutations and
Stress-Induced Replication Fork Defects in Cells Expressing
RAD51(K133A)

J 2020

TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A)

KO, Jun Ho; Mi Young SON; Qing ZHOU; Lucia MOLNÁROVÁ; Lambert SONG et. al.

Základní údaje

Originální název

TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A)

Autoři

KO, Jun Ho; Mi Young SON; Qing ZHOU; Lucia MOLNÁROVÁ; Lambert SONG; Jarmila MLCOUSKOVA; Atis JEKABSONS; Cristina MONTAGNA; Lumír KREJČÍ a Paul HASTY

Vydání

Cell Reports, Cambridge, Cell Press, 2020, 2211-1247

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10603 Genetics and heredity

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.423

Kód RIV

RIV/00216224:14310/20:00114676

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.1016/j.celrep.2020.108543

UT WoS

000601399100020

EID Scopus

2-s2.0-85098168559

Klíčová slova anglicky

DNA damage tolerance; homologous recombination; double-strand break repair; replication fork maintenance; genomic instability

Štítky

14110513, 143160, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 2. 2025 11:27, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

DNA damage tolerance (DDT) and homologous recombination (HR) stabilize replication forks (RFs). RAD18/UBC13/three prime repair exonuclease 2 (TREX2)-mediated proliferating cell nuclear antigen (PCNA) ubiqui-tination is central to DDT, an error-prone lesion bypass pathway. RAD51 is the recombinase for HR. The RAD51(K133A) mutation increased spontaneous mutations and stress-induced RF stalls and nascent strand degradation. Here, we report in RAD51(K133A) cells that this phenotype is reduced by expressing a TREX2 H188A mutation that deletes its exonuclease activity. In RAD51(K133A) cells, knocking out RAD18 or overexpressing PCNA reduces spontaneous mutations, while expressing ubiquitination-incompetent PCNA(K164R )increases mutations, indicating DDT as causal. Deleting TREX2 in cells deficient for the RF maintenance proteins poly(ADP-ribose) polymerase 1 (PARP1) or FANCB increased nascent strand degradation that was rescued by TREX2(H188A), implying that TREX2 prohibits degradation independent of catalytic activity. A possible explanation for this occurrence is that TREX2(H188A) associates with UBC13 and ubiquitinates PCNA, suggesting a dual role for TREX2 in RF maintenance.

Návaznosti

EF16_027/0008360, projekt VaV

Název: Postdoc@MUNI

GA17-17720S, projekt VaV

Název: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Grantová agentura ČR, Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

MUNI/G/1594/2019, interní kód MU

Název: RecQ4 – a protein hub required for proper replication and recombination and its implications in Rothmund-Thomson Syndrome

Investor: Masarykova univerzita, RecQ4 – a protein hub required for proper replication and recombination and its implications in Rothmund-Thomson Syndrome, INTERDISCIPLINARY - Mezioborové výzkumné projekty

21-22593X, interní kód MU

Název: Identification and characterization of proteins involved in metabolism of G-quadruplexes and R-loops and molecular mechanisms of their relationship with replication

Investor: Grantová agentura ČR, Identification and characterization of proteins involved in metabolism of G-quadruplexes and R-loops and molecular mechanisms of their relationship with replication

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

KO, Jun Ho; Mi Young SON; Qing ZHOU; Lucia MOLNÁROVÁ; Lambert SONG; Jarmila MLCOUSKOVA; Atis JEKABSONS; Cristina MONTAGNA; Lumír KREJČÍ a Paul HASTY. TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A). Cell Reports. Cambridge: Cell Press, 2020, roč. 33, č. 12, s. 1-18. ISSN 2211-1247. Dostupné z: https://doi.org/10.1016/j.celrep.2020.108543.

@article{1728144,
   author = {Ko, Jun Ho and Son, Mi Young and Zhou, Qing and Molnárová, Lucia and Song, Lambert and Mlcouskova, Jarmila and Jekabsons, Atis and Montagna, Cristina and Krejčí, Lumír and Hasty, Paul},
   article_location = {Cambridge},
   article_number = {12},
   doi = {https://doi.org/10.1016/j.celrep.2020.108543},
   keywords = {DNA damage tolerance; homologous recombination; double-strand break repair; replication fork maintenance; genomic instability},
   language = {eng},
   issn = {2211-1247},
   journal = {Cell Reports},
   title = {TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A)},
   url = {https://doi.org/10.1016/j.celrep.2020.108543},
   volume = {33},
   year = {2020}
}

TY  - JOUR
ID  - 1728144
AU  - Ko, Jun Ho - Son, Mi Young - Zhou, Qing - Molnárová, Lucia - Song, Lambert - Mlcouskova, Jarmila - Jekabsons, Atis - Montagna, Cristina - Krejčí, Lumír - Hasty, Paul
PY  - 2020
TI  - TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A)
JF  - Cell Reports
VL  - 33
IS  - 12
SP  - 1-18
EP  - 1-18
PB  - Cell Press
SN  - 22111247
KW  - DNA damage tolerance
KW  - homologous recombination
KW  - double-strand break repair
KW  - replication fork maintenance
KW  - genomic instability
UR  - https://doi.org/10.1016/j.celrep.2020.108543
L2  - https://doi.org/10.1016/j.celrep.2020.108543
N2  - DNA damage tolerance (DDT) and homologous recombination (HR) stabilize replication forks (RFs). RAD18/UBC13/three prime repair exonuclease 2 (TREX2)-mediated proliferating cell nuclear antigen (PCNA) ubiqui-tination is central to DDT, an error-prone lesion bypass pathway. RAD51 is the recombinase for HR. The RAD51(K133A) mutation increased spontaneous mutations and stress-induced RF stalls and nascent strand degradation. Here, we report in RAD51(K133A) cells that this phenotype is reduced by expressing a TREX2 H188A mutation that deletes its exonuclease activity. In RAD51(K133A) cells, knocking out RAD18 or overexpressing PCNA reduces spontaneous mutations, while expressing ubiquitination-incompetent PCNA(K164R )increases mutations, indicating DDT as causal. Deleting TREX2 in cells deficient for the RF maintenance proteins poly(ADP-ribose) polymerase 1 (PARP1) or FANCB increased nascent strand degradation that was rescued by TREX2(H188A), implying that TREX2 prohibits degradation independent of catalytic activity. A possible explanation for this occurrence is that TREX2(H188A) associates with UBC13 and ubiquitinates PCNA, suggesting a dual role for TREX2 in RF maintenance.
ER  -

KO, Jun Ho; Mi Young SON; Qing ZHOU; Lucia MOLNÁROVÁ; Lambert SONG; Jarmila MLCOUSKOVA; Atis JEKABSONS; Cristina MONTAGNA; Lumír KREJČÍ a Paul HASTY. TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A). \textit{Cell Reports}. Cambridge: Cell Press, 2020, roč.~33, č.~12, s.~1-18. ISSN~2211-1247. Dostupné z: https://doi.org/10.1016/j.celrep.2020.108543.

Přehled o publikaci