Termination of DNA synthesis by novel 3'-modified-deoxyribonucleoside 5'-triphosphates

Nucleic Acids Res. 1994 Oct 11;22(20):4259-67. doi: 10.1093/nar/22.20.4259.

Abstract

Eight 3'-modified-dNTPs were synthesized and tested in two different DNA template assays for incorporation activity. From this enzymatic screen, two 3'-O-methyl-dNTPs were shown to terminate DNA syntheses mediated by a number of polymerases and may be used as alternative terminators in Sanger sequencing. 3'-O-(2-Nitrobenzyl)-dATP is a UV sensitive nucleotide and was shown to be incorporated by several thermostable DNA polymerases. Base specific termination and efficient photolytic removal of the 3'-protecting group was demonstrated. Following deprotection, DNA synthesis was reinitiated by the incorporation of natural nucleotides into DNA. The identification of this labile terminator and the demonstration of a one cycle stop-start DNA synthesis are initial steps in the development of a novel sequencing strategy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Chromatography, High Pressure Liquid
  • DNA / biosynthesis*
  • DNA-Directed DNA Polymerase / metabolism
  • Deoxyribonucleotides / chemical synthesis
  • Deoxyribonucleotides / metabolism
  • Deoxyribonucleotides / pharmacology*
  • Molecular Sequence Data
  • Molecular Structure
  • Templates, Genetic

Substances

  • Deoxyribonucleotides
  • DNA
  • DNA-Directed DNA Polymerase