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DNA bending and torsional elasticity

DNA mechanical properties

DNA bending and torsional elasticity directly affect most, if not all, genome functions by altering the affinity of proteins for their DNA binding sites, the likelihood of protein-protein or protein-DNA interactions, the activity of DNA enzymes and DNA/chromatin packaging. We study parameters that affect DNA elasticity such as polycations, base pairing, modified DNAs, DNA bending and coating proteins, histone post-translational modifications. The figure below shows how DNA torsional curves (hat curves) obtained with magnetic tweezers can be used to study the effect of polycations on DNA torsional elasticity.

DNA topology and phase changes

DNA may undergo topological changes depending on the environment. For example, it may be condensed or extended, right- or left-handed. These different forms and the partition of DNA between them is relevant to diseases and forces in the cell play a significant role in shifting the equilibrium between these forms and phases.

Liquid-liquid condensates

This is a new area of interest in the Finzi-Dunlap group and new projects are in progress.

dna1

Publications

Authors Title Journal Volume Pages Year
Wenxuan Xu, Yan Yan, Irina Artsimovich, David Dunlap and Laura Finzi “Positive supercoiling favors transcription elongation through lac repressor-mediated DNA loops” Nucleic Acids Research 50 2826–2835 2022
Wenxuan Xu, Laura Finzi and David Dunlap “Energetics of twisted DNA topologies” Biophysical Journal 120 3242–3252 2021
Alexander Zhang, Yan Yan, Fenfei Leng, David Dunlap, and Laura Finzi “Ionic strength modulates HU protein-induced supercoiling” BIORXIV/2021/464438 2021
Yan Yan, Wenxuan Xu, Sandip Kumar, Alexander Zhang, Fenfei Leng, David D. Dunlap and Laura Finzi “Negative DNA supercoiling makes protein-mediated looping deterministic and ergodic within the bacterial doubling time” Nucleic Acids Research 49(20) 11550–11559 2021
Domenico Salerno, Francesco Mantegazza, Valeria Cassina, Matteo Cristofalo, Qing Shao, Laura Finzi, David Dunlap “Nanomechanics of negatively supercoiled diaminopurine-substituted DNA” Nucleic Acids Research 49(20) 11778–11786 2021
M. Cristofalo, D. Kovari, R. Corti, D. Salerno, V. Cassina, D. Dunlap, F. Mantegazza “Nanomechanics of diaminopurine-substituted DNA: Third hydrogen-bond stabilizes base pair interactions but facilitates conformational changes” Biophysical Journal 2019
Yan Yan, Yue Ding, David Dunlap and Laura Finzi “Protein-mediated loops in supercoiled DNA create large topological domains” Nucleic Acids Research 46(9) 4417–4424 2018
Yan Yan, Fenfei Leng, Laura Finzi and David Dunlap “Protein-mediated looping of DNA under tension requires supercoiling” Nucleic Acids Research 46(5) 2370–2379 2018
Laura Finzi and David Dunlap “Supercoiling biases the formation of loops involved in gene regulation” Biophysical Reviews 8(1) 65–74 2016
Laura Finzi and Wilma Olson “The Emerging role of DNA supercoiling as a dynamic player in genomic structure and function” Biophysical Reviews 8(1) 1–3 2016
Monica Fernandez, Qing Shao, Chandler Fountain, Laura Finzi, David D. Dunlap “E. coli gyrase fails to supercoil diaminopurine-substituted DNA negatively” JMB 427 2305–2318 2015
Yue Ding, Carlo Manzo, Geraldine Fulcrand, David Dunlap, Fenfei Leng and Laura Finzi “DNA Supercoiling: a Regulatory Signal for the Lambda Repressor” PNAS 111(43) 15402–15407 2014
Sachin Goyal, Chandler Fountain, David D. Dunlap, Fereydoon Family, Laura Finzi “Stretching DNA to quantify non-specific binding” PRE 86 011905 2012
Qing Shao, Sachin Goyal, Laura Finzi and David Dunlap “Physiological levels of salt and polyamines favor writhe and limit twist in DNA” Macromolecules 45 3188−3196 2012

Relevant Techniques

Method Used for
TPM to measure bending elasticity
MTs to measure torsional elasticity and how bending and torsional elasticity depend on the tension applied to DNA or the chromatin fiber
to measure persistence length

Complete List of Published Work in MyBibliography:

https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/40647244/?sort=date&direction=descending