Direct Genome-Scale Mapping of Human LINE-1 ORF2p Endonuclease Activity

LINE-1 is the only active protein-coding transposon in the human genome, responsible for writing more than a third of our DNA through ongoing endonuclease (EN)-dependent retrotransposition. Researchers used electronic genome mapping (EGM) to directly measure genome-scale EN nicking and determine whether EN's preferred nick site reflects intrinsic cleavage specificity or downstream reverse transcription requirements.

Using the OhmX™ Platform, the team surveyed nicking patterns of wild-type EN and a catalytically inactive control across Lambda, E. coli, and human genomic DNA. Nicking was confirmed at canonical consensus sequences—and new sequence motifs were identified, suggesting EN's sequence preference in genomic DNA is broader than insertion site analyses indicate.

Explore how direct, genome-scale profiling of endonuclease activity with EGM opens new avenues for characterizing DNA nicking and modification at scale.