The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations Journal Article
| Authors: | Wray, J.; Williamson, E. A.; Chester, S.; Farrington, J.; Sterk, R.; Weinstock, D. M.; Jasin, M.; Lee, S. H.; Nickoloff, J. A.; Hromas, R. |
| Article Title: | The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations |
| 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. © 2010 Elsevier Inc. |
| Keywords: | protein expression; leukemia; unclassified drug; dna-binding proteins; nonhuman; polymerase chain reaction; biological marker; animal cell; mouse; animals; mice; dna repair; enzyme activity; carcinogenesis; recombinant fusion proteins; histone-lysine n-methyltransferase; immunoprecipitation; plasmid; murinae; chromosome translocation; translocation, genetic; molecular interaction; animal cell culture; polydeoxyribonucleotide synthase; primate; nih 3t3 cells; marker gene; dna ligases; primates; metnase protein; setmar protein; transposase; enzyme repression; nonhomologous end joining; transposases; simiiformes |
| Journal Title: | Cancer Genetics and Cytogenetics |
| Volume: | 200 |
| Issue: | 2 |
| ISSN: | 0165-4608 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2010-07-01 |
| Start Page: | 184 |
| End Page: | 190 |
| Language: | English |
| DOI: | 10.1016/j.cancergencyto.2010.04.011 |
| PUBMED: | 20620605 |
| PROVIDER: | scopus |
| PMCID: | PMC2904321 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: CGCYD" - "Source: Scopus" |
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