Regulation of Metnase's TIR binding activity by its binding partner, Pso4

Brian D. Beck, Sung S. Lee, Robert Hromas, Suk-Hee Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Metnase (also known as SETMAR) is a SET and transposase fusion protein in humans and plays a positive role in double-strand break (DSB) repair. While the SET domain possesses histone lysine methyltransferase activity, the transposase domain is responsible for 5'-terminal inverted repeat (TIR)-specific binding, DNA looping, and DNA cleavage activities. We recently demonstrated that human homolog of Pso4 (hPso4) is a Metnase binding partner that mediates Metnase binding to non-TIR DNA such as DNA damage sites. Here we show that Metnase functions as a dimer in its TIR binding. While both Metnase and hPso4 can independently interact with TIR DNA, Metnase's DNA binding activity is not required for formation of the Metnase-hPso4-DNA complex. A further stoichiometric analysis indicated that only one protein is involved in interaction with dsDNA when Metnase-hPso4 forms a stable complex. Interaction of the Metnase-hPso4 complex with TIR DNA was competitively inhibited by both TIR and non-TIR DNA, suggesting that hPso4 is solely responsible for binding to DNA in the Metnase-hPso4-DNA complex. Together, our study suggests that hPso4, once it forms a complex with Metnase, negatively regulates Metnase's TIR binding activity, which is perhaps necessary for Metnase localization at non-TIR sites such as DSBs.

Original languageEnglish
Pages (from-to)89-94
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume498
Issue number2
DOIs
StatePublished - Jun 2010

Fingerprint

Terminal Repeat Sequences
DNA
Transposases
Histone-Lysine N-Methyltransferase
DNA Cleavage
DNA Damage
Proteins
Dimers
Repair
Fusion reactions

Keywords

  • DNA binding
  • DNA repair
  • HPso4
  • Metnase
  • SETMAR
  • Transposase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Regulation of Metnase's TIR binding activity by its binding partner, Pso4. / Beck, Brian D.; Lee, Sung S.; Hromas, Robert; Lee, Suk-Hee.

In: Archives of Biochemistry and Biophysics, Vol. 498, No. 2, 06.2010, p. 89-94.

Research output: Contribution to journalArticle

Beck, Brian D. ; Lee, Sung S. ; Hromas, Robert ; Lee, Suk-Hee. / Regulation of Metnase's TIR binding activity by its binding partner, Pso4. In: Archives of Biochemistry and Biophysics. 2010 ; Vol. 498, No. 2. pp. 89-94.
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