Asymmetric base-pair opening drives helicase unwinding dynamics

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-pai...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 116; no. 45; pp. 22471 - 22477
Main Authors Colizzi, Francesco, Perez-Gonzalez, Cibran, Fritzen, Remi, Levy, Yaakov, White, Malcolm F., Penedo, J. Carlos, Bussi, Giovanni
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 05.11.2019
Subjects
Asymmetry
Bacteria - enzymology
Bacteria - genetics
Bacteria - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Base Pairing
Base Sequence
Bases (nucleic acids)
Biological Sciences
Deoxyribonucleic acid
DNA
DNA helicase
DNA Helicases - genetics
DNA Helicases - metabolism
DNA, Bacterial - chemistry
DNA, Bacterial - genetics
Gene expression
Gene regulation
Kinetics
Physical Sciences
Pyrimidines
Ribonucleic acid
RNA
RNA, Bacterial - genetics
RNA, Bacterial - metabolism
Substrates
Transcription
Unwinding
nucleic acids
unwindability
double helix
experiments
simulations
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by Hashim M. Al-Hashimi, Duke University Medical Center, Durham, NC, and accepted by Editorial Board Member Stephen J. Benkovic September 23, 2019 (received for review January 19, 2019)
Author contributions: F.C. and G.B. conceived the study; F.C., J.C.P., and G.B. designed research; F.C., C.P.-G., R.F., J.C.P., and G.B. performed research; F.C., M.F.W., J.C.P., and G.B. contributed new reagents/analytic tools; F.C., C.P.-G., R.F., Y.L., M.F.W., J.C.P., and G.B. analyzed data; C.P.-G., R.F., Y.L., and M.F.W. provided inputs for the manuscript; and F.C., J.C.P., and G.B. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1901086116