DNA sequencing with chain-terminating inhibitors
Sanger, Nicklen, and Coulson introduced a new method for determining nucleotide sequences in DNA, building on their earlier 'plus and minus' technique. The method uses 2′,3′-dideoxy and arabinonucleoside analogues of the normal deoxynucleoside triphosphates, which act as specific chain-terminating inhibitors of DNA polymerase, generating a set of partially extended chains that can be size-separated by gel electrophoresis to read the sequence. Applied to bacteriophage φX174 DNA, the approach proved faster and more accurate than the original plus or minus method.