Single-molecule polarization microscopy of DNA intercalators sheds light on the structure of S-DNA

Backer, Adam S.; Biebricher, Andreas S.; King, Graeme A.; Wuite, Gijs J. L.; Heller, Iddo; Peterman, Erwin J. G.

doi:10.1126/sciadv.aav1083

Single-molecule polarization microscopy of DNA intercalators sheds light on the structure of S-DNA

Journal Article · Fri Mar 22 00:00:00 EDT 2019 · Science Advances

DOI:https://doi.org/10.1126/sciadv.aav1083· OSTI ID:1644083

Backer, Adam S. ^[1]; Biebricher, Andreas S. ^[2]; ^[2]; ^[2]; ^[2]; ^[2]

Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Vrije Univ. Amsterdam (Netherlands)

DNA structural transitions facilitate genomic processes, mediate drug-DNA interactions, and inform the development of emerging DNA-based biotechnology such as programmable materials and DNA origami. While some features of DNA conformational changes are well characterized, fundamental information such as the orientations of the DNA base pairs is unknown. Here, we use concurrent fluorescence polarization imaging and DNA manipulation experiments to probe the structure of S-DNA, an elusive, elongated conformation that can be accessed by mechanical overstretching. To this end, we directly quantify the orientations and rotational dynamics of fluorescent DNA-intercalated dyes. At extensions beyond the DNA overstretching transition, intercalators adopt a tilted (θ ~ 54°) orientation relative to the DNA axis, distinct from the nearly perpendicular orientation (θ ~ 90°) normally assumed at lower extensions. These results provide the first experimental evidence that S-DNA has substantially inclined base pairs relative to those of the standard (Watson-Crick) B-DNA conformation.

View Accepted Manuscript (DOE)

Research Organization:: Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); Harry S. Truman Fellowship; Netherlands Organization for Scientific Research (NWO); Human Frontier Science Program; LASERLAB-EUROPE; USDOE Laboratory Directed Research and Development (LDRD) Program

Grant/Contract Number:: AC04-94AL85000; NA0003525

OSTI ID:: 1644083

Report Number(s):: SAND--2020-7446J; 687512

Journal Information:: Science Advances, Journal Name: Science Advances Journal Issue: 3 Vol. 5; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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