Faculty Collaboration Database

Target-site preferences of Sleeping Beauty transposons. J Mol Biol 2005 Feb 11;346(1):161-73

Date

01/25/2005

Pubmed ID

15663935

DOI

10.1016/j.jmb.2004.09.086

Scopus ID

2-s2.0-19944431736 (requires institutional sign-in at Scopus site)   117 Citations

Abstract

The Sleeping Beauty (SB) transposon is a Tc1/mariner family transposon that has applications in vertebrate animals for gene transfer, gene-tagging, and human gene therapy. In this study, we analyzed the target-site preferences of the SB transposon. At the genomic level, integration of SB transposons with respect to genes (exons and introns) and intergenic regions appears fairly random but not on a micro-scale. Although there appears to be a consensus sequence around the vicinity of the target sites, the primary sequence is not the determining factor for target selection. When integrations were examined over a limited topography, the sites used most often for integration did not match the consensus sequence. Rather, a unique deformation inherent in the sequence may be a recognition signal for target selection. The deformation is characterized by an angling of the target site such that the axis around the insertion site is off-center, the rotation of the helix (twisting) is non-uniform and there is an increase in the distance between the central base-pairs. Our observations offer several hypothetical insights into the transposition process. Our observations suggest that particular deformations of the double helix predicted by the V(step) algorithm can distinguish TA sites that vary by about 16-fold in their preferences for accommodating insertions of SB transposons.

Author List

Liu G, Geurts AM, Yae K, Srinivasan AR, Fahrenkrug SC, Largaespada DA, Takeda J, Horie K, Olson WK, Hackett PB

Author

Aron Geurts PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

AT Rich Sequence
Base Sequence
DNA
DNA Transposable Elements
Humans
Mutagenesis, Insertional
Nucleic Acid Conformation
Recombination, Genetic
Substrate Specificity
Transposases