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Beneficial and detrimental effects of non-specific binding during DNA hybridization.

Tam T M PhanTien M PhanJeremy D Schmit
Published in: Biophysical journal (2023)
DNA strands have to sample numerous states to find the alignment that maximizes Watson-Crick-Franklin base pairing. This process depends strongly on sequence, which affects the stability of the native duplex as well as the prevalence of non-native inter- and intramolecular helices. We present a theory that describes DNA hybridization as a three-stage process: diffusion, registry search, and zipping. We find that non-specific binding affects each of these stages in different ways. Mis-registered intermolecular binding in the registry search stage helps DNA strands sample different alignments and accelerates the hybridization rate. Non-native intramolecular structure affects all three stages by rendering portions of the molecule inert to intermolecular association, limiting mis-registered alignments to be sampled, and impeding the zipping process. Once in-register base pairs are formed, the stability of the native structure is important to hold the molecules together long enough for non-native contacts to break.
Keyphrases
  • single molecule
  • circulating tumor
  • nucleic acid
  • cell free
  • energy transfer
  • dna binding
  • circulating tumor cells
  • transcription factor
  • quantum dots