Biochemical characterization of metnases endonuclease activity and its role in NHEJ repair

Brian D. Beck, Sung Sook Lee, Elizabeth Williamson, Robert A. Hromas, Suk Hee Lee

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Abstract

Metnase (SETMAR) is a SET-transposase fusion protein that promotes nonhomologous end joining (NHEJ) repair in humans. Although both SET and the transposase domains were necessary for its function in DSB repair, it is not clear what specific role Metnase plays in the NHEJ. In this study, we show that Metnase possesses a unique endonuclease activity that preferentially acts on ssDNA and ssDNA-overhang of a partial duplex DNA. Cell extracts lacking Metnase poorly supported DNA end joining, and addition of wt-Metnase to cell extracts lacking Metnase markedly stimulated DNA end joining, while a mutant (D483A) lacking endonuclease activity did not. Given that Metnase overexpression enhanced DNA end processing in vitro, our finding suggests a role for Metnases endonuclease activity in promoting the joining of noncompatible ends.

Original languageEnglish (US)
Pages (from-to)4360-4370
Number of pages11
JournalBiochemistry
Volume50
Issue number20
DOIs
StatePublished - May 24 2011

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Beck, B. D., Lee, S. S., Williamson, E., Hromas, R. A., & Lee, S. H. (2011). Biochemical characterization of metnases endonuclease activity and its role in NHEJ repair. Biochemistry, 50(20), 4360-4370. https://doi.org/10.1021/bi200333k