The Human SETMAR Protein Preserves Most of the Activities of the Ancestral <i>Hsmar1</i> Transposase

Liu, Danxu; Bischerour, Julien; Siddique, Azeem; Buisine, Nicolas; Bigot, Yves; Chalmers, Ronald

doi:10.1128/mcb.01899-06

Cited by 96 publications

(173 citation statements)

References 42 publications

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“…Others have shown that this domain has some but not all of the characteristics of transposases [14][15][16]. Here we found that this domain was also important for assisting in lentiviral genomic integration, a function not unlike transposition.…”

Section: Resultssupporting

confidence: 51%

Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration

et al. 2008

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We recently identified a Transposase domain protein called Metnase, which assists in repairing DNA double-strand breaks (DSB) via non-homologous end-joining (NHEJ), and is important for foreign DNA integration into a host cell genome. Since integration is essential for productive lentiviral infection we examined whether Metnase expression levels could have an influence on lentiviral genomic integration. Using cells stably transduced to either over-or under-express Metnase we determined that the expression level of Metnase did indeed correlate with live lentiviral integration. Changes in Metnase levels were accompanied by changes in the number of copies of integrated lentiviral cDNA. While Metnase levels affected lentiviral integration, it had no effect on the amount of either total cellular viral RNA, cDNA or 2-LTR circles. Therefore, Metnase enhances the integration of lentivirus DNA into the host cell genome.

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Section: Resultssupporting

confidence: 51%

Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration

et al. 2008

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“…The human SETMAR protein binds Hsmar1 IRs and retains 5 cleavage activity of its transposase domain. The transposase domain of the SETMAR protein was recently shown to specifically bind to Hsmar1 IRs (5) and to catalyze transposition reactions in vitro (32). Since the protein used in those experiments lacked the SET domain, we addressed the question of whether the full-length physiological form of SETMAR can also exhibit transposase-related activities.…”

Section: Resultsmentioning

confidence: 99%

“…The 83-bp-long probe comprising the 5Ј IR of Hsmar1 was obtained by annealing the primers Hsmar1/Apo1 and Hsmar1/AflII, followed by a Klenow fill-in reaction using [␣-P 32 ]dATP (Perkin Elmer); 0.24 pmol of MBP-Hsmar1-Ra or 2.5 pmol of MBP-SETMAR was incubated with 0.3 pmol of probe in a 20-l binding reaction mixture as described previously (32) for 3 h at room temperature. The binding reaction products were separated on 6% Tris-acetic acid-polyacrylamide gels containing VOL.…”

Section: Methodsmentioning

confidence: 99%

“…The SETMAR protein has been shown to have histone H3 methyltransferase activity in vitro and has been proposed to play a role in DNA double-strand break (DSB) repair (30). Both the transposase domain of SETMAR and the full-length SETMAR protein were shown to bind to Hsmar1 IR sequences (5,32), and it was recently demonstrated that SETMAR can perform transposition reactions using precleaved transposon substrates in vitro (32).…”

mentioning

confidence: 99%

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The Ancient mariner Sails Again: Transposition of the Human Hsmar1 Element by a Reconstructed Transposase and Activities of the SETMAR Protein on Transposon Ends

Miskey

Papp

Mátés

et al. 2007

Molecular and Cellular Biology

112

136

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Hsmar1, one of the two subfamilies of mariner transposons in humans, is an ancient element that entered the primate genome lineage ϳ50 million years ago. Although Hsmar1 elements are inactive due to mutational damage, one particular copy of the transposase gene has apparently been under selection. This transposase coding region is part of the SETMAR gene, in which a histone methylatransferase SET domain is fused to an Hsmar1 transposase domain. A phylogenetic approach was taken to reconstruct the ancestral Hsmar1 transposase gene, which we named Hsmar1-Ra. The Hsmar1-Ra transposase efficiently mobilizes Hsmar1 transposons by a cut-and-paste mechanism in human cells and zebra fish embryos. Hsmar1-Ra can also mobilize short inverted-repeat transposable elements (MITEs) related to Hsmar1 (MiHsmar1), thereby establishing a functional relationship between an Hsmar1 transposase source and these MITEs. MiHsmar1 excision is 2 orders of magnitude more efficient than that of long elements, thus providing an explanation for their high copy numbers. We show that the SETMAR protein binds and introduces single-strand nicks into Hsmar1 invertedrepeat sequences in vitro. Pathway choices for DNA break repair were found to be characteristically different in response to transposon cleavage mediated by Hsmar1-Ra and SETMAR in vivo. Whereas nonhomologous end joining plays a dominant role in repairing excision sites generated by the Hsmar1-Ra transposase, DNA repair following cleavage by SETMAR predominantly follows a homology-dependent pathway. The novel transposon system can be a useful tool for genome manipulations in vertebrates and for investigations into the transpositional dynamics and the contributions of these elements to primate genome evolution.

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“…The best studied example is the RAG1 gene that evolved from the Transib superfamily of DNA transposons (15) and that, together with RAG2, carries out V(D)J recombination, a site-directed DNA rearrangement of Ig gene segments in vertebrates (16). The primate-specific SETMAR gene that arose by fusion of a mariner transposase gene and a SET chromatin modifier domain has conserved some activities of the transposase, including binding and cleaving transposon ends (17)(18)(19).…”

mentioning

confidence: 99%

Transposition of a reconstructed Harbinger element in human cells and functional homology with two transposon-derived cellular genes

Sinzelle

Kapitonov

Grzela

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

107

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The Human SETMAR Protein Preserves Most of the Activities of the Ancestral Hsmar1 Transposase

Cited by 96 publications

References 42 publications

Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration

Expression levels of the human DNA repair protein metnase influence lentiviral genomic integration

The Ancient mariner Sails Again: Transposition of the Human Hsmar1 Element by a Reconstructed Transposase and Activities of the SETMAR Protein on Transposon Ends

Transposition of a reconstructed Harbinger element in human cells and functional homology with two transposon-derived cellular genes

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