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 (703 Slovensko, domácí), Lambert SONG, Jarmila MLCOUSKOVA, Atis JEKABSONS (428 Lotyšsko, domácí), Cristina MONTAGNA, Lumír KREJČÍ (203 Česká republika, domácí) 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

http://dx.doi.org/10.1016/j.celrep.2020.108543

UT WoS

000601399100020

Klíčová slova anglicky

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

Štítky

14110513, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 3. 2021 13:59, Mgr. Tereza Miškechová

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

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://dx.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 = {http://dx.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://dx.doi.org/10.1016/j.celrep.2020.108543.

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