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Nucleic Acids Research, 1989, Vol. 17, No. 11 4223-4233
© 1989

CHEMISTRY

Chemical reactivity of matched cytosine and thymine bases near mismatched and unmatched bases in a heteroduplex between DNA strands with multiple differences

Richard G.H. Cotton* and R.Duncan Campbell1

1MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford Oxford OX1 3QU, UK Murdoch Institute, Royal Children's Hospital Melbourne 3052, Australia

*To whom correspondence should be addressed

Received March 21, 1989. Revised May 10, 1989. Accepted May 10, 1989.

The chemical reactivity of matched T and C bases to osmium tetroxide and hydroxylamine near mismatched and unmatched bases in a heteroduplex between two strands of DNA with multiple differences was examined. Data was available for matched bases one or two positions away from 24 mismatches. Reactive bases were found near 16 of the mismatches and were usually one or two bases away. This reactivity is consistant with structural studies indicating perturbation of the duplex around mismatches and will allow another mode of study of the effect of mismatches. The reactivity of these bases was found not to be strongly correlated with mismatch type or GC basepair content of the basepairs around the mismatches. Extra reactivity may have been promoted by the presence of either T or C in the mismatch allowing increased reactivity of nearby T or C. The utility of the phenomenon for the detection of mutations is discussed. Unmatched bases in the heteroduplex also gives rise to reactive matched bases nearby.


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