Zheleva, AngelinaPérez de Camino Cantos, DoloresFernández Fernández, NuriaGarcía Rubio, María LuisaAskjaer, PeterGarcía Muse, TatianaAguilera López, Andrés2021-09-282021-09-282021Zheleva, A., Pérez de Camino Cantos, D., Fernández Fernández, N., García Rubio, M.L., Askjaer, P., García Muse, T. y Aguilera López, A. (2021). C. elegans THSC/TREX-2 deficiency causes replication stress and genome instability. Journal of Cell Science, jcs.258435.1477-91370021-9533https://hdl.handle.net/11441/126250Transcription is an essential process of DNA metabolism, yet it makes DNA more susceptible to DNA damage. THSC/TREX-2 is a conserved eukaryotic protein complex with a key role in mRNP biogenesis and maturation that prevents genome instability. One source of such instability is linked to transcription as shown in yeast and human cells, but the underlying mechanism and whether is universal is still unclear. To get further insight in the putative role of THSC/TREX-2 in genome integrity we have used Caenorhabditis elegans mutants of the THP-1 and DSS-1 members of THSC/TREX-2. These mutants show similar defective meiosis, DNA damage accumulation and activation of the DNA damage checkpoint. However, they differ regarding replication defects as determined by dUTP incorporation in the germline. Interestingly, this specific thp-1 phenotype can be partially rescued by overexpression of RNase H. Furthermore, both mutants show a mild increase in the H3S10P mark previously shown to be linked to DNA-RNA hybrid-mediated genome instability. These data support the view that both THSC/TREX-2 factors prevent transcription-associated DNA damage derived from DNA-RNA hybrid accumulation by separate means.application/pdf34 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/C. elegansDNA-RNA hybridsGenome instabilityReplicationTHSC/TREX-2 complexinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1242/jcs.258435