Article
VID22 counteracts G-quadruplex-induced genome instability
Author/s | Galati, Elena
Bosio, Maria C. Novarina, Daniele Chiara, Matteo Bernini, Giulia M. Mozzarelli, Alessandro M. García Rubio, María Luisa Gómez González, Belén Aguilera López, Andrés Carzaniga, Thomas Todisco, Marco Bellini, Tommaso Nava, Giulia M. Frige, Gianmaria Lazzaro, Federico |
Department | Universidad de Sevilla. Departamento de Genética |
Publication Date | 2021 |
Deposit Date | 2022-01-28 |
Published in |
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Abstract | Genome 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, ... Genome 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. |
Project ID. | 15631
21806 PRIN 2015- 2015SJLMB9 PRIN 2017-2017KSZZJW PRIN2017-2017Z55KC BFU2016- 75058-P FDN-159913 |
Citation | Galati, 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. |
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