Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair

J Biol Chem. 2008 Apr 4;283(14):9023-30. doi: 10.1074/jbc.M800150200. Epub 2008 Feb 8.

Abstract

Metnase, also known as SETMAR, is a SET and transposase fusion protein with an undefined role in mammalian DNA repair. The SET domain is responsible for histone lysine methyltransferase activity at histone 3 K4 and K36, whereas the transposase domain possesses 5'-terminal inverted repeat (TIR)-specific DNA binding, DNA looping, and DNA cleavage activities. Although the transposase domain is essential for Metnase function in DNA repair, it is not clear how a protein with sequence-specific DNA binding activity plays a role in DNA repair. Here, we show that human homolog of the ScPSO4/PRP19 (hPso4) forms a stable complex with Metnase on both TIR and non-TIR DNA. The transposase domain essential for Metnase-TIR interaction is not sufficient for its interaction with non-TIR DNA in the presence of hPso4. In vivo, hPso4 is induced and co-localized with Metnase following ionizing radiation treatment. Cells treated with hPso4-siRNA failed to show Metnase localization at DSB sites and Metnase-mediated stimulation of DNA end joining coupled to genomic integration, suggesting that hPso4 is necessary to bring Metnase to the DSB sites for its function(s) in DNA repair.

Publication types

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

MeSH terms

  • Cell Line
  • DNA Breaks, Double-Stranded*
  • DNA Repair / physiology*
  • DNA Repair Enzymes / antagonists & inhibitors
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism
  • Humans
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Structure, Tertiary / physiology
  • RNA Splicing Factors
  • RNA, Small Interfering / genetics
  • Terminal Repeat Sequences / physiology*

Substances

  • DNA-Binding Proteins
  • Histones
  • Nuclear Proteins
  • RNA Splicing Factors
  • RNA, Small Interfering
  • Histone-Lysine N-Methyltransferase
  • SETMAR protein, human
  • DNA Repair Enzymes
  • PRPF19 protein, human