hnRNP-U is a specific DNA-dependent protein kinase substrate phosphorylated in response to DNA double-strand breaks

Biochem Biophys Res Commun. 2009 Mar 27;381(1):59-64. doi: 10.1016/j.bbrc.2009.02.019. Epub 2009 Feb 11.

Abstract

Cellular responses to DNA damage are orchestrated by the large phosphoinositol-3-kinase related kinases ATM, ATR and DNA-PK. We have developed a cell-free system to dissect the biochemical mechanisms of these kinases. Using this system, we identify heterogeneous nuclear ribonucleoprotein U (hnRNP-U), also termed scaffold attachment factor A (SAF-A), as a specific substrate for DNA-PK. We show that hnRNP-U is phosphorylated at Ser59 by DNA-PK in vitro and in cells in response to DNA double-strand breaks. Phosphorylation of hnRNP-U suggests novel functions for DNA-PK in the response to DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell-Free System / enzymology
  • Checkpoint Kinase 1
  • DNA Breaks, Double-Stranded*
  • DNA-Activated Protein Kinase / metabolism*
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation
  • Heterogeneous-Nuclear Ribonucleoprotein U / metabolism*
  • Humans
  • Molecular Sequence Data
  • Phosphorylation
  • Poly dA-dT / metabolism
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Serine / metabolism*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Heterogeneous-Nuclear Ribonucleoprotein U
  • Tumor Suppressor Proteins
  • Poly dA-dT
  • Serine
  • Protein Kinases
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Checkpoint Kinase 1
  • DNA-Activated Protein Kinase
  • Protein Serine-Threonine Kinases