DOI: 10.1101/470427Nov 14, 2018Paper

PP4 phosphatase cooperates in recombinational DNA repair by enhancing double-strand break end resection

BioRxiv : the Preprint Server for Biology
María Teresa VilloriaAndrés Clemente-Blanco

Abstract

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 the Mec1 kinase and its own auto-phosphorylation in a manner dependent on the adaptor Rad9. While the mechanism behind Rad53 phosphorylation and activation has been well documented, less is known about the processes that counteract its kinase activity during the response to DNA damage. Here, we describe that PP4 phosphatase dephosphorylates Rad53 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 DNA resection and repair by single-strand annealing, defects that are bypassed by reducing the hyper-phosphorylation state of Rad53 observed in the absence of the phosphatase. These results confirm that Rad53 is one of the main targets of PP4 during the repair of a DNA lesion and demonstrate that the attenuation of its kinase activity during the initial steps of the re...Continue Reading

Related Concepts

DNA
DNA Damage
Phosphoric Monoester Hydrolases
Phosphorylation
Phosphotransferases
Rad9 protein
SGS1 protein, S cerevisiae
DNA, Double-Stranded
Excision
Response to DNA Damage Stimulus

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