The Ku complex promotes DNA end-bridging and this function is antagonized by Tel1/ATM kinase.
DNA
/ metabolism
DNA Breaks, Double-Stranded
DNA End-Joining Repair
DNA Repair
DNA-Binding Proteins
/ genetics
Intracellular Signaling Peptides and Proteins
/ genetics
Ku Autoantigen
/ metabolism
Nucleosomes
Protein Serine-Threonine Kinases
/ metabolism
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
28 02 2023
28 02 2023
Historique:
accepted:
20
01
2023
revised:
18
01
2023
received:
27
06
2022
pubmed:
11
2
2023
medline:
4
3
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
DNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or non-homologous end-joining (NHEJ). NHEJ is induced by the binding to DSBs of the Ku70-Ku80 heterodimer, which acts as a hub for the recruitment of downstream NHEJ components. An important issue in DSB repair is the maintenance of the DSB ends in close proximity, a function that in yeast involves the MRX complex and Sae2. Here, we provide evidence that Ku contributes to keep the DNA ends tethered to each other. The ku70-C85Y mutation, which increases Ku affinity for DNA and its persistence very close to the DSB ends, enhances DSB end-tethering and suppresses the end-tethering defect of sae2Δ cells. Impairing histone removal around DSBs either by eliminating Tel1 kinase activity or nucleosome remodelers enhances Ku persistence at DSBs and DSB bridging, suggesting that Tel1 antagonizes the Ku function in supporting end-tethering by promoting nucleosome removal and possibly Ku sliding inwards. As Ku provides a block to DSB resection, this Tel1 function can be important to regulate the mode by which DSBs are repaired.
Identifiants
pubmed: 36762474
pii: 7033796
doi: 10.1093/nar/gkad062
pmc: PMC9976877
doi:
Substances chimiques
DNA
9007-49-2
DNA-Binding Proteins
0
Intracellular Signaling Peptides and Proteins
0
Ku Autoantigen
EC 4.2.99.-
Nucleosomes
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Saccharomyces cerevisiae Proteins
0
TEL1 protein, S cerevisiae
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1783-1802Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
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