TY - JOUR
T1 - Supercoiling DNA Locates Mismatches
AU - Dittmore, Andrew
AU - Brahmachari, Sumitabha
AU - Takagi, Yasuharu
AU - Marko, John F.
AU - Neuman, Keir C.
N1 - Funding Information:
This work was supported by in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. Work at NU was supported by the NIH through Grants No. R01-GM105847 and No. U54-CA193419 (CR-PS-OC) and a subcontract to Grant No. U54-DK107980, and by the NSF through Grants No. MCB-1022117 and No. DMR-1206868.
Publisher Copyright:
© 2017 American Physical Society.
PY - 2017/10/3
Y1 - 2017/10/3
N2 - We present a method of detecting sequence defects by supercoiling DNA with magnetic tweezers. The method is sensitive to a single mismatched base pair in a DNA sequence of several thousand base pairs. We systematically compare DNA molecules with 0 to 16 adjacent mismatches at 1 M monovalent salt and 3.6 pN force and show that under these conditions, a single plectoneme forms and is stably pinned at the defect. We use these measurements to estimate the energy and degree of end-loop kinking at defects. From this, we calculate the relative probability of plectoneme pinning at the mismatch under physiologically relevant conditions. Based on this estimate, we propose that DNA supercoiling could contribute to mismatch and damage sensing in vivo.
AB - We present a method of detecting sequence defects by supercoiling DNA with magnetic tweezers. The method is sensitive to a single mismatched base pair in a DNA sequence of several thousand base pairs. We systematically compare DNA molecules with 0 to 16 adjacent mismatches at 1 M monovalent salt and 3.6 pN force and show that under these conditions, a single plectoneme forms and is stably pinned at the defect. We use these measurements to estimate the energy and degree of end-loop kinking at defects. From this, we calculate the relative probability of plectoneme pinning at the mismatch under physiologically relevant conditions. Based on this estimate, we propose that DNA supercoiling could contribute to mismatch and damage sensing in vivo.
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U2 - 10.1103/PhysRevLett.119.147801
DO - 10.1103/PhysRevLett.119.147801
M3 - Article
C2 - 29053317
AN - SCOPUS:85030749554
SN - 0031-9007
VL - 119
JO - Physical Review Letters
JF - Physical Review Letters
IS - 14
M1 - 147801
ER -