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VID22 counteracts G-quadruplex-induced genome instability.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2021 Dec 16; Vol. 49 (22), pp. 12785-12804. - Publication Year :
- 2021
-
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, 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.<br /> (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Subjects :
- Chromosome Aberrations
DNA Damage
Genome, Fungal
Membrane Proteins genetics
Membrane Proteins metabolism
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins genetics
Saccharomyces cerevisiae Proteins metabolism
Telomere Homeostasis
G-Quadruplexes
Genomic Instability
Membrane Proteins physiology
Saccharomyces cerevisiae Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 49
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 34871443
- Full Text :
- https://doi.org/10.1093/nar/gkab1156