PP4 phosphatase cooperates in recombinational DNA repair by enhancing double-strand break end resection.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 11 2019
18 11 2019
Historique:
accepted:
11
09
2019
revised:
30
08
2019
received:
09
05
2019
pubmed:
24
9
2019
medline:
13
5
2020
entrez:
24
9
2019
Statut:
ppublish
Résumé
The role of Rad53 in response to a DNA lesion is central for the accurate orchestration of the DNA damage response. Rad53 activation relies on its phosphorylation by Mec1 and its own autophosphorylation in a manner dependent on the adaptor Rad9. While the mechanism behind Rad53 activation has been well documented, less is known about the processes that counteract its activity along the repair of a DNA adduct. Here, we describe that PP4 phosphatase is required to avoid Rad53 hyper-phosphorylation during the repair of a double-strand break, a process that impacts on the phosphorylation status of multiple factors involved in the DNA damage response. PP4-dependent Rad53 dephosphorylation stimulates DNA end resection by relieving the negative effect that Rad9 exerts over the Sgs1/Dna2 exonuclease complex. Consequently, elimination of PP4 activity affects resection and repair by single-strand annealing, defects that are bypassed by reducing Rad53 hyperphosphorylation. These results confirm that Rad53 phosphorylation is controlled by PP4 during the repair of a DNA lesion and demonstrate that the attenuation of its kinase activity during the initial steps of the repair process is essential to efficiently enhance recombinational DNA repair pathways that depend on long-range resection for their success.
Identifiants
pubmed: 31544936
pii: 5572570
doi: 10.1093/nar/gkz794
pmc: PMC6846210
doi:
Substances chimiques
DNA, Fungal
0
Saccharomyces cerevisiae Proteins
0
Phosphoserine
17885-08-4
PPH3 protein, S cerevisiae
EC 3.1.3.16
Phosphoprotein Phosphatases
EC 3.1.3.16
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10706-10727Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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