Abstract:<\/p>\n
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) ubiquitination 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 RAD51K133A\u00a0cells that this phenotype is reduced by expressing a TREX2 H188A mutation that deletes its exonuclease activity. In RAD51K133A\u00a0cells, knocking out RAD18 or overexpressing PCNA reduces spontaneous mutations, while expressing ubiquitination-incompetent PCNAK164R\u00a0increases 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 TREX2H188A, implying that TREX2 prohibits degradation independent of catalytic activity. A possible explanation for this occurrence is that TREX2H188Aassociates with UBC13 and ubiquitinates PCNA, suggesting a dual role for TREX2 in RF maintenance.<\/p>\n
Jun Ho Ko, Mi Young Son, Qing Zhou, Lucia Molnarova, Lambert Song, Jarmila Mlcouskova, Atis Jekabsons, Cristina Montagna, Lumir Krejci, Paul Hasty<\/p>\n
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Cell Rep\u00a02020 Dec 22;33(12):108543. doi: 10.1016\/j.celrep.2020.108543.<\/p>\n
<\/p>\n","protected":false},"excerpt":{"rendered":"
Abstract: 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) ubiquitination 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. […]<\/p>\n","protected":false},"author":264,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"class_list":["post-1419","post","type-post","status-publish","format-standard","hentry","category-highimpactpublication"],"yoast_head":"\n