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

Resultado de la investigación: Articlerevisión exhaustiva

25 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)184-190
Número de páginas7
PublicaciónCancer Genetics and Cytogenetics
Volumen200
N.º2
DOI
EstadoPublished - jul. 2010
Publicado de forma externa

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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