SQ/TQ Cluster Domains: Concentrated ATM/ATR Kinase Phosphorylation Site Regions in DNA-damage-response Proteins

Bioessays. 2005 Apr;27(4):397-407. doi: 10.1002/bies.20204.

Abstract

ATM/ATR-like protein kinases play central roles in the maintenance of genome stability and phosphorylate numerous substrates in response to DNA damage, preferentially on SQ or TQ motifs. ATM/ATR substrates often contain several closely spaced SQ/TQ motifs in regions that have been termed SQ/TQ cluster domains (SCDs). SCDs are now considered a structural hallmark of DNA-damage-response proteins. Mutational analyses of a number of SCD-containing proteins indicate that multisite phosphorylation of SQ/TQ motifs is required for normal DNA-damage responses, most commonly by mediating protein-protein interactions in the formation of DNA-damage-induced complexes. SCD sequences are highly diverse and these domains may be largely unfolded in their native state rather than adopting a common three-dimensional fold. Structural disorder of SCDs could be advantageous for efficient phosphorylation by ATM/ATR kinases and also enable them to be molded into distinct conformations to facilitate flexible interactions with multiple binding partners.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Motifs*
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Checkpoint Kinase 1
  • Checkpoint Kinase 2
  • DNA Damage*
  • DNA Mutational Analysis
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Phosphorylation
  • Protein Conformation
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Protein Kinases
  • Checkpoint Kinase 2
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK2 protein, human
  • Checkpoint Kinase 1
  • Protein-Serine-Threonine Kinases