The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations

Justin Wray, Elizabeth A. Williamson, Sean Chester, Jacqueline Farrington, Rosa Sterk, David M. Weinstock, Maria Jasin, Suk Hee Lee, Jac A. Nickoloff, Robert Hromas

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Chromosomal translocations are common in leukemia, but little is known about their mechanism. Metnase (also termed SETMAR) is a fusion of a histone methylase and transposase protein that arose specifically in primates. Transposases were thought to be extinct in primates because they would mediate deleterious DNA movement. In primates, Metnase interacts with DNA Ligase IV (Lig IV) and promotes nonhomologous end-joining (NHEJ) DNA repair. We show here that the primate-specific protein Metnase can also enhance NHEJ in murine cells and can also interact with murine Lig IV, indicating that it integrated into the preexisting NHEJ pathway after its development in primates. Significantly, expressing Metnase in murine cells significantly reduces chromosomal translocations. We propose that the fusion of the histone methylase SET domain and the transposase domain in the anthropoid lineage to form primate Metnase promotes accurate intrachromosomal NHEJ and thereby suppresses interchromosomal translocations. Metnase may have been selected for because it has a function opposing transposases and may thus play a key role in suppressing translocations that underlie oncogenicity.

Original languageEnglish (US)
Pages (from-to)184-190
Number of pages7
JournalCancer Genetics and Cytogenetics
Volume200
Issue number2
DOIs
StatePublished - Jul 1 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Wray, J., Williamson, E. A., Chester, S., Farrington, J., Sterk, R., Weinstock, D. M., Jasin, M., Lee, S. H., Nickoloff, J. A., & Hromas, R. (2010). The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations. Cancer Genetics and Cytogenetics, 200(2), 184-190. https://doi.org/10.1016/j.cancergencyto.2010.04.011