VID22 counteracts G-quadruplex-induced genome instability.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
16 12 2021
16 12 2021
Historique:
accepted:
08
11
2021
revised:
19
10
2021
received:
03
06
2021
pubmed:
7
12
2021
medline:
27
1
2022
entrez:
6
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34871443
pii: 6454281
doi: 10.1093/nar/gkab1156
pmc: PMC8682794
doi:
Substances chimiques
Membrane Proteins
0
Saccharomyces cerevisiae Proteins
0
VID22 protein, S cerevisiae
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12785-12804Subventions
Organisme : Telethon
ID : GGP15227
Pays : Italy
Organisme : CIHR
ID : FDN-159913
Pays : Canada
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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