Profiling DNA damage-induced phosphorylation in budding yeast reveals diverse signaling networks Academic Article uri icon

Overview

MeSH Major

  • DNA Damage
  • Saccharomyces cerevisiae
  • Signal Transduction

abstract

  • The DNA damage response (DDR) is regulated by a protein kinase signaling cascade that orchestrates DNA repair and other processes. Identifying the substrate effectors of these kinases is critical for understanding the underlying physiology and mechanism of the response. We have used quantitative mass spectrometry to profile DDR-dependent phosphorylation in budding yeast and genetically explored the dependency of these phosphorylation events on the DDR kinases MEC1, RAD53, CHK1, and DUN1. Based on these screens, a database containing many novel DDR-regulated phosphorylation events has been established. Phosphorylation of many of these proteins has been validated by quantitative peptide phospho-immunoprecipitation and examined for functional relevance to the DDR through large-scale analysis of sensitivity to DNA damage in yeast deletion strains. We reveal a link between DDR signaling and the metabolic pathways of inositol phosphate and phosphatidyl inositol synthesis, which are required for resistance to DNA damage. We also uncover links between the DDR and TOR signaling as well as translation regulation. Taken together, these data shed new light on the organization of DDR signaling in budding yeast.

publication date

  • June 28, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4932963

Digital Object Identifier (DOI)

  • 10.1073/pnas.1602827113

PubMed ID

  • 27298372

Additional Document Info

start page

  • E3667

end page

  • 75

volume

  • 113

number

  • 26