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Intron-encoded endonuclease I-SceI, commonly known as I-SceI meganuclease, is a site-specific homing endonuclease originally identified in the mitochondria of the yeast Saccharomyces cerevisiae [1]. It belongs to the LAGLIDADG family of proteins and is renowned for its ability to recognize and cleave a highly specific 18-base pair asymmetric DNA sequence (5'-TAGGGATAACAGGGTAAT-3'), a sequence so rare it is statistically unlikely to occur naturally in the human genome [2]. This extreme specificity allows I-SceI to serve as a precise molecular scalpel, inducing targeted double-strand breaks (DSBs) that activate cellular DNA repair mechanisms like homology-directed repair (HDR) or non-homologous end joining (NHEJ) [3][4]. While newer technologies like CRISPR/Cas9 offer greater flexibility, I-SceI remains a critical gold standard for studying DNA repair kinetics and developing gene correction therapies for genetic disorders [5]. In a therapeutic context, I-SceI is utilized as a component of gene editing platforms to disrupt viral DNA or facilitate gene replacement, though its clinical use is limited by the requirement for its specific recognition site [6]. Safety considerations include potential off-target effects at near-match sequences and the immunogenicity of the yeast-derived protein when introduced into human patients [4][5].
Induces site-specific DNA double-strand breaks (DSBs) at an 18-base pair recognition sequence, triggering cellular DNA repair mechanisms such as non-homologous end joining (NHEJ) or homology-directed repair (HDR) to achieve targeted genome modification [1][2][4].
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