Galati, ElenaBosio, Maria C.Novarina, DanieleChiara, MatteoBernini, Giulia M.Mozzarelli, Alessandro M.García Rubio, María LuisaGómez González, BelénAguilera López, AndrésCarzaniga, ThomasTodisco, MarcoBellini, TommasoNava, Giulia M.Frige, GianmariaLazzaro, Federico2022-01-282022-01-282021Galati, E., Bosio, M.C., Novarina, D., Chiara, M., Bernini, G.M., Mozzarelli, A.M.,...,Lazzaro, F. (2021). VID22 counteracts G-quadruplex-induced genome instability. Nucleic Acids Research, 49 (22), 12785-12804.0305-10481362-4962https://hdl.handle.net/11441/129420Genome instability is a condition characterized by the accumulation of genetic alterations and is a hallmark of cancer cells. To uncover new genes and cellular pathways affecting endogenous DNA damage and genome integrity, we exploited a Synthetic Genetic Array (SGA)-based screen in yeast. Among the positive genes, we identified VID22, reported to be involved in DNA double-strand break repair. vid22Δ cells exhibit increased levels of endogenous DNA damage, chronic DNA damage response activation and accumulate DNA aberrations in sequences displaying high probabilities of forming G-quadruplexes (G4-DNA). If not resolved, these DNA secondary structures can block the progression of both DNA and RNA polymerases and correlate with chromosome fragile sites. Vid22 binds to and protects DNA at G4-containing regions both in vitro and in vivo. Loss of VID22 causes an increase in gross chromosomal rearrangement (GCR) events dependent on G-quadruplex forming sequences. Moreover, the absence of Vid22 causes defects in the correct maintenance of G4-DNA rich elements, such as telomeres and mtDNA, and hypersensitivity to the G4-stabilizing ligand TMPyP4. We thus propose that Vid22 is directly involved in genome integrity maintenance as a novel regulator of G4 metabolism.application/pdf20 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.1093/nar/gkab1156