Farmacología

URI permanente para esta comunidadhttps://hdl.handle.net/11441/11024

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DDX47, MeCP2, and other functionally heterogeneous factors protect cells from harmful R loops
(Elsevier, 2023) Marchena Cruz, Esther; Camino, Lola P.; Bhandari, Jay; Pinela Da Silva, Sonia Cristina; Marqueta Gracia, José Javier; Amdeen, Shahad A.; Guillén Mendoza, Cristina; García Rubio, María Luisa; Calderón Montaño, José Manuel; Xue, Xiaoyu; Luna Varo, Rosa María; Aguilera López, Andrés; Universidad de Sevilla. Departamento de Genética; Universidad de Sevilla. Departamento de Farmacología; Ministerio de Ciencia e Innovación (MICIN). España; European Research Council (ERC); Ministerio de Economía y Competitividad (MINECO). España
Unscheduled R loops can be a source of genome instability, a hallmark of cancer cells. Although targeted proteomic approaches and cellular analysis of specific mutants have uncovered factors potentially involved in R-loop homeostasis, we report a more open screening of factors whose depletion causes R loops based on the ability of activation-induced cytidine deaminase (AID) to target R loops. Immunofluorescence analysis of gH2AX caused by small interfering RNAs (siRNAs) covering 3,205 protein-coding genes identifies 59 potential candidates, from which 13 are analyzed further and show a significant increase of R loops. Such candidates are enriched in factors involved in chromatin, transcription, and RNA biogenesis and other processes. A more focused study shows that the DDX47 helicase is an R-loop resolvase, whereas the MeCP2 methyl-CpG-binding protein uncovers a link between DNA methylation and R loops. Thus, our results suggest that a plethora of gene dysfunctions can alter cell physiology via affecting R-loop homeostasis by different mechanisms.

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Examinando Farmacología por Autor "Aguilera López, Andrés"