Sequence-Dependent Deviations of Constrained DNA from Canonical B‑Form

Decades of crystallographic and NMR studies have produced canonical structural models of short DNA. However, no experimental method so far has been able to test these models in vivo, where DNA is long and constrained by interactions with membranes, proteins, and other molecules. Here, we employ high...

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Published inNano letters Vol. 19; no. 9; pp. 6600 - 6603
Main Authors Kuchuk, Kfir, Katrivas, Liat, Kotlyar, Alexander, Sivan, Uri
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 11.09.2019
Subjects
Bacteriophage lambda - chemistry
DNA, B-Form - chemistry
DNA, Viral - chemistry
Models, Molecular
Nucleic Acid Conformation
Poly dA-dT - chemistry
AFM
single molecule biophysics
DNA
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Abstract Decades of crystallographic and NMR studies have produced canonical structural models of short DNA. However, no experimental method so far has been able to test these models in vivo, where DNA is long and constrained by interactions with membranes, proteins, and other molecules. Here, we employ high-resolution frequency-modulation AFM to image single long poly­(dA)-poly­(dT), poly­(dG)-poly­(dC), and lambda DNA molecules interacting with an underlying substrate that emulates the effect of biological constraints on molecular structure. We find systematic sequence-dependent variations in groove dimensions, indicating that the structure of DNA subject to realistic interactions may differ profoundly from canonical models. These findings highlight the value of AFM as a unique, single molecule characterization tool.
AbstractList Decades of crystallographic and NMR studies have produced canonical structural models of short DNA. However, no experimental method so far has been able to test these models in vivo, where DNA is long and constrained by interactions with membranes, proteins, and other molecules. Here, we employ high-resolution frequency-modulation AFM to image single long poly(dA)-poly(dT), poly(dG)-poly(dC), and lambda DNA molecules interacting with an underlying substrate that emulates the effect of biological constraints on molecular structure. We find systematic sequence-dependent variations in groove dimensions, indicating that the structure of DNA subject to realistic interactions may differ profoundly from canonical models. These findings highlight the value of AFM as a unique, single molecule characterization tool.
Decades of crystallographic and NMR studies have produced canonical structural models of short DNA. However, no experimental method so far has been able to test these models in vivo, where DNA is long and constrained by interactions with membranes, proteins, and other molecules. Here, we employ high-resolution frequency-modulation AFM to image single long poly­(dA)-poly­(dT), poly­(dG)-poly­(dC), and lambda DNA molecules interacting with an underlying substrate that emulates the effect of biological constraints on molecular structure. We find systematic sequence-dependent variations in groove dimensions, indicating that the structure of DNA subject to realistic interactions may differ profoundly from canonical models. These findings highlight the value of AFM as a unique, single molecule characterization tool.
Decades of crystallographic and NMR studies have produced canonical structural models of short DNA. However, no experimental method so far has been able to test these models in vivo, where DNA is long and constrained by interactions with membranes, proteins, and other molecules. Here, we employ high-resolution frequency-modulation AFM to image single long poly(dA)-poly(dT), poly(dG)-poly(dC), and lambda DNA molecules interacting with an underlying substrate that emulates the effect of biological constraints on molecular structure. We find systematic sequence-dependent variations in groove dimensions, indicating that the structure of DNA subject to realistic interactions may differ profoundly from canonical models. These findings highlight the value of AFM as a unique, single molecule characterization tool.Decades of crystallographic and NMR studies have produced canonical structural models of short DNA. However, no experimental method so far has been able to test these models in vivo, where DNA is long and constrained by interactions with membranes, proteins, and other molecules. Here, we employ high-resolution frequency-modulation AFM to image single long poly(dA)-poly(dT), poly(dG)-poly(dC), and lambda DNA molecules interacting with an underlying substrate that emulates the effect of biological constraints on molecular structure. We find systematic sequence-dependent variations in groove dimensions, indicating that the structure of DNA subject to realistic interactions may differ profoundly from canonical models. These findings highlight the value of AFM as a unique, single molecule characterization tool.
Author Kotlyar, Alexander
Kuchuk, Kfir
Sivan, Uri
Katrivas, Liat
AuthorAffiliation Department of Physics and the Russell Berrie Nanotechnology Institute
Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences and the Center of Nanoscience and Nanotechnology
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SubjectTerms Bacteriophage lambda - chemistry
DNA, B-Form - chemistry
DNA, Viral - chemistry
Models, Molecular
Nucleic Acid Conformation
Poly dA-dT - chemistry
Title Sequence-Dependent Deviations of Constrained DNA from Canonical B‑Form
URI http://dx.doi.org/10.1021/acs.nanolett.9b02863
https://www.ncbi.nlm.nih.gov/pubmed/31424224
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