Metnase/SETMAR: A domesticated primate transposase that enhances DNA repair, replication, and decatenation

Montaser Shaheen, Elizabeth Williamson, Jac Nickoloff, Suk Hee Lee, Robert Hromas

Research output: Contribution to journalReview article

33 Scopus citations

Abstract

Metnase is a fusion gene comprising a SET histone methyl transferase domain and a transposase domain derived from the Mariner transposase. This fusion gene appeared first in anthropoid primates. Because of its biochemical activities, both histone (protein) methylase and endonuclease, we termed the protein Metnase (also called SETMAR). Metnase methylates histone H3 lysine 36 (H3K36), improves the integration of foreign DNA, and enhances DNA double-strand break (DSB) repair by the non-homologous end joining (NHEJ) pathway, potentially dependent on its interaction with DNA Ligase IV. Metnase interacts with PCNA and enhances replication fork restart after stalling. Metnase also interacts with and stimulates TopoIIα-dependent chromosome decatenation and regulates cellular sensitivity to topoisomerase inhibitors used as cancer chemotherapeutics. Metnase has DNA nicking and endonuclease activity that linearizes but does not degrade supercoiled plasmids. Metnase has many but not all of the properties of a transposase, including Terminal Inverted Repeat (TIR) sequence-specific DNA binding, DNA looping, paired end complex formation, and cleavage of the 5′ end of a TIR, but it cannot efficiently complete transposition reactions. Interestingly, Metnase suppresses chromosomal translocations. It has been hypothesized that transposase activity would be deleterious in primates because unregulated DNA movement would predispose to malignancy. Metnase may have been selected for in primates because of its DNA repair and translocation suppression activities. Thus, its transposase activities may have been subverted to prevent deleterious DNA movement.

Original languageEnglish (US)
Pages (from-to)559-566
Number of pages8
JournalGenetica
Volume138
Issue number5
DOIs
StatePublished - May 1 2010

Keywords

  • Decatenation
  • DNA repair
  • DNA replication
  • Histone methylation
  • Metnase
  • Setmar
  • Transposase
  • Transposon

ASJC Scopus subject areas

  • Genetics
  • Insect Science
  • Animal Science and Zoology
  • Plant Science

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