Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response

Nat Rev Mol Cell Biol. 2013 Sep;14(9):563-80. doi: 10.1038/nrm3640.


Coordinated progression through the cell cycle is a complex challenge for eukaryotic cells. Following genotoxic stress, diverse molecular signals must be integrated to establish checkpoints specific for each cell cycle stage, allowing time for various types of DNA repair. Phospho-Ser/Thr-binding domains have emerged as crucial regulators of cell cycle progression and DNA damage signalling. Such domains include 14-3-3 proteins, WW domains, Polo-box domains (in PLK1), WD40 repeats (including those in the E3 ligase SCF(βTrCP)), BRCT domains (including those in BRCA1) and FHA domains (such as in CHK2 and MDC1). Progress has been made in our understanding of the motif (or motifs) that these phospho-Ser/Thr-binding domains connect with on their targets and how these interactions influence the cell cycle and DNA damage response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Cycle / genetics
  • DNA Damage
  • DNA Repair
  • Humans
  • Models, Molecular
  • Phosphoserine / chemistry*
  • Phosphoserine / metabolism
  • Phosphothreonine / chemistry*
  • Phosphothreonine / metabolism
  • Protein Binding
  • Protein Structure, Tertiary*
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism


  • Proteins
  • Phosphothreonine
  • Phosphoserine