Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Sequential primed kinases create a damage-responsive phosphodegron on Eco1

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Lyons, N. A.
  • Fonslow, B. R.
  • Diedrich, J. K.
  • Yates III, John
  • Morgan, D. O.

publication date

  • February 2013

journal

  • Nature Structural & Molecular Biology  Journal

abstract

  • Sister-chromatid cohesion is established during S phase when Eco1 acetylates cohesin. In budding yeast, Eco1 activity falls after S phase due to Cdk1-dependent phosphorylation, which triggers ubiquitination by SCF(Cdc4). We show here that Eco1 degradation requires the sequential actions of Cdk1 and two additional kinases, Cdc7-Dbf4 and the GSK-3 homolog Mck1. These kinases recognize motifs primed by previous phosphorylation, resulting in an ordered sequence of three phosphorylation events on Eco1. Only the latter two phosphorylation sites are spaced correctly to bind Cdc4, resulting in strict discrimination between phosphates added by Cdk1 and by Cdc7. Inhibition of Cdc7 by the DNA damage response prevents Eco1 destruction, allowing establishment of cohesion after S phase. This elaborate regulatory system, involving three independent kinases and stringent substrate selection by a ubiquitin ligase, enables robust control of cohesion establishment during normal growth and after stress.

subject areas

  • Acetyltransferases
  • Blotting, Western
  • CDC2 Protein Kinase
  • Cell Cycle Proteins
  • Chromatids
  • Chromosomal Proteins, Non-Histone
  • DNA Damage
  • F-Box Proteins
  • Fluorescence Polarization
  • Glycogen Synthase Kinase 3
  • Mass Spectrometry
  • Nuclear Proteins
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • Proteolysis
  • S Phase
  • Saccharomyces cerevisiae Proteins
  • Substrate Specificity
  • Ubiquitin-Protein Ligases
scroll to property group menus

Identity

PubMed Central ID

  • PMC3565030

International Standard Serial Number (ISSN)

  • 1545-9993

Digital Object Identifier (DOI)

  • 10.1038/nsmb.2478

PubMed ID

  • 23314252
scroll to property group menus

Additional Document Info

start page

  • 194

end page

  • 201

volume

  • 20

issue

  • 2

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support