The human L1 endonuclease (L1EN) is encoded by the L1 non-LTR retrotransposon that is responsible for more than 1.5 million genomic re-integration events resulting in more than a quarter of our genomic DNA.
We have determined the crystal structure of human L1EN and have suggested a model for DNA binding. (Weichenrieder et al, Structure 2004). Based on this model and on structure-based endonuclease alignments we constructed loop-graft mutants and tested them in vitro and in vivo and showed their effect on tagrget sequence specificity (Repanas et al, NAR 2007).
Our results aim to provide further insight both into the mechanism and into the specificity of L1EN. We anticipate that this work will facilitate attempts to modulate the sequence specificity of any
given endonuclease, e.g. to convert the respective retrotransposon into a genetic tool for i.e. gene therapy.
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