Rad4 recognition-at-a-distance: Physical basis of conformation-specific anomalous diffusion of DNA repair proteins

Kong, Muwen; Houten, Bennett Van

doi:10.1016/j.pbiomolbio.2016.12.004

Cited by 27 publications

(21 citation statements)

References 122 publications

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“…Furthermore, the increase in anomalous subdiffusion on DNA, which we term constrained motion, has been recently observed for the Rad4-Rad23 nucleotide excision repair damage sensor ( 47 ). Thus, constrained motion may be a general feature of damage searching for DNA repair enzymes ( 58 ). Multiple theoretical models have been extensively studied to model and describe experimentally observed anomalous subdiffusion in membranes or systems with molecular crowding effects ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

PARP1 changes from three-dimensional DNA damage searching to one-dimensional diffusion after auto-PARylation or in the presence of APE1

Liu

Kong

Gassman

et al. 2017

Nucleic Acids Research

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PARP1-dependent poly-ADP-ribosylation (PARylation) participates in the repair of many forms of DNA damage. Here, we used atomic force microscopy (AFM) and single molecule fluorescence microscopy to examine the interactions of PARP1 with common DNA repair intermediates. AFM volume analysis indicates that PARP1 binds to DNA at nicks, abasic (AP) sites, and ends as a monomer. Single molecule DNA tightrope assays were used to follow the real-time dynamic behavior of PARP1 in the absence and presence of AP endonuclease (APE1) on AP DNA damage arrays. These experiments revealed that PARP1 conducted damage search mostly through 3D diffusion. Co-localization of APE1 with PARP1 on DNA was found capable of inducing 1D diffusion of otherwise nonmotile PARP1, while excess APE1 also facilitated the dissociation of DNA-bound PARP1. Moreover, auto-PARylation of PARP1 allowed the protein to switch its damage search strategy by causing a 3-fold increase in linear diffusion. Finally, we demonstrated that PARP inhibitor olaparib did not significantly alter the rate of PARP1 dissociation from DNA, but instead resulted in more motility of DNA-bound PARP1 molecules.

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Section: Discussionmentioning

confidence: 99%

PARP1 changes from three-dimensional DNA damage searching to one-dimensional diffusion after auto-PARylation or in the presence of APE1

Liu

Kong

Gassman

et al. 2017

Nucleic Acids Research

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“…The research field of anomalous diffusion and transport [1][2][3][4][5][6][7][8][9][10][11] currently flourishes getting ever more experimental support and manifestations in such diverse research areas as transport processes in living cells and polymeric solutions , colloidal systems [12,15,43,44], dust plasmas [45], organic photoconductors [46], conformational diffusion in proteins [47][48][49][50][51][52][53][54][55][56], self-diffusion in lipid bilayers [57][58][59], diffusion of proteins on DNA strands [60][61][62], to name just a few. Differently from normal diffusion, α = 1, the variance of the diffusing particle positions, δx 2 (t) ∝ t α , often grows sublinearly, α < 1, or superlinearly, α > 1, in time, with some power law exponent α.…”

Section: Introductionmentioning

confidence: 99%

Viscoelastic subdiffusion in a random Gaussian environment

Goychuk

2018

Phys. Chem. Chem. Phys.

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Viscoelastic subdiffusion governed by a fractional Langevin equation is studied numerically in a random Gaussian environment modeled by stationary Gaussian potentials with decaying spatial correlations. This anomalous diffusion is archetypal for living cells, where cytoplasm is known to be viscoelastic and a spatial disorder also naturally emerges. We obtain some first important insights into it within a model one-dimensional study. Two basic types of potential correlations are studied: short-range exponentially decaying and algebraically slow decaying with an infinite correlation length, both for a moderate (several kT, in the units of thermal energy), and strong (5-10kT) disorder. For a moderate disorder, it is shown that on the ensemble level viscoelastic subdiffusion can easily overcome the medium's disorder. Asymptotically, it is not distinguishable from the disorder-free subdiffusion. However, a strong scatter in single-trajectory averages is nevertheless seen even for a moderate disorder. It features a weak ergodicity breaking, which occurs on a very long yet transient time scale. Furthermore, for a strong disorder, a very long transient regime of logarithmic, Sinai-type diffusion emerges. It can last longer and be faster in the absolute terms for weakly decaying correlations as compared with the short-range correlations. Residence time distributions in a finite spatial domain are of a generalized log-normal type and are reminiscent also of a stretched exponential distribution. They can be easily confused for power-law distributions in view of the observed weak ergodicity breaking. This suggests a revision of some experimental data and their interpretation.

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“…Super-diffusion (red), random diffusion (blue), sub-diffusion (green). Adapted with permission from [11]. (F) Modes of protein-DNA interaction.…”

Section: Single Molecule Assays Focusing On Dna Repairmentioning

confidence: 99%

Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes

et al. 2019

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Genomes are constantly in flux, undergoing changes due to recombination, repair and mutagenesis. In vivo, many of such changes are studies using reporters for specific types of changes, or through cytological studies that detect changes at the single-cell level. Single molecule assays, which are reviewed here, can detect transient intermediates and dynamics of events. Biochemical assays allow detailed investigation of the DNA and protein activities of each step in a repair, recombination or mutagenesis event. Each type of assay is a powerful tool but each comes with its particular advantages and limitations. Here the most commonly used assays are reviewed, discussed, and presented as the guidelines for future studies.

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Rad4 recognition-at-a-distance: Physical basis of conformation-specific anomalous diffusion of DNA repair proteins

Cited by 27 publications

References 122 publications

PARP1 changes from three-dimensional DNA damage searching to one-dimensional diffusion after auto-PARylation or in the presence of APE1

PARP1 changes from three-dimensional DNA damage searching to one-dimensional diffusion after auto-PARylation or in the presence of APE1

Viscoelastic subdiffusion in a random Gaussian environment

Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes

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