The Nup84 complex coordinates the DNA damage response to warrant genome integrity.
DNA Breaks, Double-Stranded
/ radiation effects
DNA Repair
DNA Replication
/ radiation effects
DNA, Fungal
/ genetics
Genome, Fungal
Genomic Instability
Nuclear Pore
/ metabolism
Nuclear Pore Complex Proteins
/ deficiency
Protein Isoforms
/ genetics
Rad52 DNA Repair and Recombination Protein
/ genetics
S Phase Cell Cycle Checkpoints
/ genetics
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Sister Chromatid Exchange
Ultraviolet Rays
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
07 05 2019
07 05 2019
Historique:
accepted:
25
01
2019
revised:
24
01
2019
received:
21
06
2018
pubmed:
5
2
2019
medline:
26
11
2019
entrez:
5
2
2019
Statut:
ppublish
Résumé
DNA lesions interfere with cellular processes such as transcription and replication and need to be adequately resolved to warrant genome integrity. Beyond their primary role in molecule transport, nuclear pore complexes (NPCs) function in other processes such as transcription, nuclear organization and DNA double strand break (DSB) repair. Here we found that the removal of UV-induced DNA lesions by nucleotide excision repair (NER) is compromised in the absence of the Nup84 nuclear pore component. Importantly, nup84Δ cells show an exacerbated sensitivity to UV in early S phase and delayed replication fork progression, suggesting that unrepaired spontaneous DNA lesions persist during S phase. In addition, nup84Δ cells are defective in the repair of replication-born DSBs by sister chromatid recombination (SCR) and rely on post-replicative repair functions for normal proliferation, indicating dysfunctions in the cellular pathways that enable replication on damaged DNA templates. Altogether, our data reveal a central role of the NPC in the DNA damage response to facilitate replication progression through damaged DNA templates by promoting efficient NER and SCR and preventing chromosomal rearrangements.
Identifiants
pubmed: 30715474
pii: 5306206
doi: 10.1093/nar/gkz066
pmc: PMC6486642
doi:
Substances chimiques
DNA, Fungal
0
NUP84 protein, S cerevisiae
0
Nuclear Pore Complex Proteins
0
Protein Isoforms
0
RAD52 protein, S cerevisiae
0
Rad52 DNA Repair and Recombination Protein
0
Saccharomyces cerevisiae Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4054-4067Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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