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DNA ligases seal 5′-PO4 and three′-OH polynucleotide finishes by way of a few nucleotidyl transfer techniques involving ligase-adenylate and DNA-adenylate intermediates. DNA ligases are essential guardians of genomic integrity, and ligase dysfunction underlies human genetic disease syndromes. Crystal constructions of DNA ligases certain to nucleotide and nucleic acid substrates have illuminated how ligase reaction chemistry is catalyzed, how ligases identify ruined DNA ends, and how protein area movements and Lively-site transforming are accustomed to choreograph the end-joining pathway.
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An engineered stage three arrest mutant of DNA ligase would, if extensively active, pepper the genome with unresected five′-adenylates at sites of DNA repair or joining of Okazaki fragments. This would be catastrophic if the level of DNA five′-adenylylation exceeds the mobile's potential to eliminate the lesions (33). This kind of situation is analogous to “poisoning” of topoisomerase IB by camptothecin medication or drug-mimetic enzyme mutations that selectively impede the DNA ligation phase of the topoisomerase pathway.
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