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

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F20%3A00114676" target="_blank" >RIV/00216224:14310/20:00114676 - isvavai.cz</a>
Alternative codes found
RIV/00159816:_____/20:00073490
Result on the web
<a href="https://doi.org/10.1016/j.celrep.2020.108543" target="_blank" >https://doi.org/10.1016/j.celrep.2020.108543</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.celrep.2020.108543" target="_blank" >10.1016/j.celrep.2020.108543</a>

Result language
angličtina
Original language name
TREX2 Exonuclease Causes Spontaneous Mutations and Stress-Induced Replication Fork Defects in Cells Expressing RAD51(K133A)
Original language description
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.
Czech name
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Czech description
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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
10603 - Genetics and heredity (medical genetics to be 3)

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

Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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