DNA binding and transposition activity of the Sleeping Beauty transposase: role of structural stability of the primary DNA-binding domain

DNA transposons have emerged as promising tools in both gene therapy and functional genomics. In particular, the Sleeping Beauty (SB) DNA transposon has advanced into clinical trials due to its ability to stably integrate DNA sequences of choice into eukaryotic genomes. The efficiency of the DNA tra...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2024-12
Main Authors: Ranjan, Venkatesh V, Leighton, Gage O, Yan, Chenbo, Arango, Maria, Lustig, Janna, Corona, Rosario I, Guo, Jun-Tao, Nesmelov, Yuri E, Ivics, Zoltán, Nesmelova, Irina V
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:DNA transposons have emerged as promising tools in both gene therapy and functional genomics. In particular, the Sleeping Beauty (SB) DNA transposon has advanced into clinical trials due to its ability to stably integrate DNA sequences of choice into eukaryotic genomes. The efficiency of the DNA transposon system depends on the interaction between the transposon DNA and the transposase enzyme that facilitates gene transfer. In this study, we assess the DNA-binding capabilities of variants of the SB transposase and demonstrate that the structural stability of the primary DNA-recognition subdomain, PAI, affects SB DNA-binding affinity and transposition activity. This fundamental understanding of the structure-function relationship of the SB transposase will assist the design of improved transposases for gene therapy applications.
ISSN:1362-4962
1362-4962
DOI:10.1093/nar/gkae1188