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Science 13 December 1991:
Vol. 254. no. 5038, pp. 1639 - 1642
DOI: 10.1126/science.1836279
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Articles

Science, Vol 254, Issue 5038, 1639-1642
Copyright © 1991 by American Association for the Advancement of Science

articles

Site-specific cleavage of human chromosome 4 mediated by triple-helix formation

SA Strobel, LA Doucette-Stamm, L Riba, DE Housman, and PB Dervan

Arnold and Mabel Beckman Laboratories of Chemical Synthesis, California Institute of Technology, Pasadena 91125.

Direct physical isolation of specific DNA segments from the human genome is a necessary goal in human genetics. For testing whether triple-helix mediated enzymatic cleavage can liberate a specific segment of a human chromosome, the tip of human chromosome 4, which contains the entire candidate region for the Huntington's disease gene, was chosen as a target. A 16-base pyrimidine oligodeoxyribonucleotide was able to locate a 16-base pair purine target site within more than 10 gigabase pairs of genomic DNA and mediate the exact enzymatic cleavage at that site in more than 80 percent yield. The recognition motif is sufficiently generalizable that most cosmids should contain a sequence targetable by triple-helix formation. This method may facilitate the orchestrated dissection of human chromosomes from normal and affected individuals into megabase sized fragments and facilitate the isolation of candidate gene loci.


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