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High-resolution structure of a DNA helix containing mismatched base pairs Tom Brown*, Olga Kennard*, Geoff Kneale* & Dov Rabinovich†
*University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK
†The Weizmann Institute of Science, Rehovot 76100, Israel
The concept of complementary base pairing, integral to the double-helical structure of DNA, provides an effective and elegant mechanism for the faithful transmission of genetic information1,2. Implicit in this model, however, is the potential for incorporating non-complementary base pairs (mismatches) during replication or subsequently, for example, during genetic recombination3,4. As such errors are usually damaging to the organism, they are generally detected and repaired. Occasionally, however, the propagation of erroneous copies of the genome confers a selective advantage, leading to genetic variation and evolutionary change. An understanding of the nature of base-pair mismatches at a molecular level, and the effect of incorporation of such errors on the secondary structure of DNA is thus of fundamental importance. We now report the first single-crystal X-ray analysis of a DNA fragment, d(GGGGCTCC), which contains two non-complementary G T base pairs, and discuss the implications of the results for the in vivo recognition of base-pair mismatches.
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