Asymmetric base-pair opening drives helicase unwinding dynamics

Francesco Colizzi*, Cibran Perez-Gonzalez, Remi Fritzen, Yaakov Levy, Malcolm F. White, J. Carlos Penedo*, Giovanni Bussi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The opening of a Watson–Crick double helix is required for crucial cellular processes, including replication, repair, and transcription. It has long been assumed that RNA or DNA base pairs are broken by the concerted symmetric movement of complementary nucleobases. By analyzing thousands of base-pair opening and closing events from molecular simulations, here, we uncover a systematic stepwise process driven by the asymmetric flipping-out probability of paired nucleobases. We demonstrate experimentally that such asymmetry strongly biases the unwinding efficiency of DNA helicases toward substrates that bear highly dynamic nucleobases, such as pyrimidines, on the displaced strand. Duplex substrates with identical thermodynamic stability are thus shown to be more easily unwound from one side than the other, in a quantifiable and predictable manner. Our results indicate a possible layer of gene regulation coded in the direction-dependent unwindability of the double helix.
Original languageEnglish
Pages (from-to)22471-22477
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number45
Early online date18 Oct 2019
DOIs
Publication statusPublished - 5 Nov 2019

Keywords

  • Double helix
  • Nucleic acids
  • Simulations
  • Experiments
  • Unwindability

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