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As a strategy to promote site-directed recombination, a bis-PNA was coupled to a 40-nt donor DNA fragment homologous to an adjacent region in the target gene. The PNA\u2013DNA conjugate was found to mediate site-directed recombination with a plasmid substrate in human cell-free extracts, resulting in correction of a mutation in a reporter gene at a frequency at least 60-fold above background. Induced site-specific recombination was also seen when the bis-PNA and the donor DNA were co-mixed without covalent linkage. In addition, the bis-PNA and the bis-PNA\u2013DNA conjugate were found to induce DNA repair specifically in the target plasmid. Both the PNA-induced recombination and the PNA-induced repair were found to be dependent on the nucleotide excision repair factor, XPA (xeroderma pigmentosum complementation group A protein). These results suggest that the formation of a PNA clamp on duplex DNA creates a helical distortion that strongly provokes DNA repair and thereby sensitizes the target site to recombination. The ability to promote recombination in a site-directed manner using PNA\u2013DNA conjugates may provide a useful strategy to achieve targeted correction of defective genes.<\/jats:p>","DOI":"10.1073\/pnas.262556899","type":"journal-article","created":{"date-parts":[[2002,12,23]],"date-time":"2002-12-23T13:14:48Z","timestamp":1040649288000},"page":"16695-16700","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":104,"title":["Site-directed recombination via bifunctional PNA\u2013DNA conjugates"],"prefix":"10.1073","volume":"99","author":[{"given":"Faye A.","family":"Rogers","sequence":"first","affiliation":[{"name":"Departments of Therapeutic Radiology and Genetics, Yale University School of Medicine, New Haven, CT 06520; Department of Carcinogenesis, University of Texas M. D. 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