TY - JOUR
T1 - Single-Molecule Microscopy Meets Molecular Dynamics Simulations for Characterizing the Molecular Action of Proteins on DNA and in Liquid Condensates
AU - Kamagata, Kiyoto
N1 - Funding Information:
This work was supported by MEXT/JSPS KAKENHI (20K06571 and 21H00379).
Publisher Copyright:
Copyright © 2021 Kamagata.
PY - 2021/11/19
Y1 - 2021/11/19
N2 - DNA-binding proteins trigger various cellular functions and determine cellular fate. Before performing functions such as transcription, DNA repair, and DNA recombination, DNA-binding proteins need to search for and bind to their target sites in genomic DNA. Under evolutionary pressure, DNA-binding proteins have gained accurate and rapid target search and binding strategies that combine three-dimensional search in solution, one-dimensional sliding along DNA, hopping and jumping on DNA, and intersegmental transfer between two DNA molecules. These mechanisms can be achieved by the unique structural and dynamic properties of these proteins. Single-molecule fluorescence microscopy and molecular dynamics simulations have characterized the molecular actions of DNA-binding proteins in detail. Furthermore, these methodologies have begun to characterize liquid condensates induced by liquid-liquid phase separation, e.g., molecular principles of uptake and dynamics in droplets. This review discusses the molecular action of DNA-binding proteins on DNA and in liquid condensate based on the latest studies that mainly focused on the model protein p53.
AB - DNA-binding proteins trigger various cellular functions and determine cellular fate. Before performing functions such as transcription, DNA repair, and DNA recombination, DNA-binding proteins need to search for and bind to their target sites in genomic DNA. Under evolutionary pressure, DNA-binding proteins have gained accurate and rapid target search and binding strategies that combine three-dimensional search in solution, one-dimensional sliding along DNA, hopping and jumping on DNA, and intersegmental transfer between two DNA molecules. These mechanisms can be achieved by the unique structural and dynamic properties of these proteins. Single-molecule fluorescence microscopy and molecular dynamics simulations have characterized the molecular actions of DNA-binding proteins in detail. Furthermore, these methodologies have begun to characterize liquid condensates induced by liquid-liquid phase separation, e.g., molecular principles of uptake and dynamics in droplets. This review discusses the molecular action of DNA-binding proteins on DNA and in liquid condensate based on the latest studies that mainly focused on the model protein p53.
KW - diffusion
KW - intrinsically disordered protein
KW - liquid-liquid phase separation
KW - molecular dynamics
KW - single-molecule
KW - sliding
KW - target search
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U2 - 10.3389/fmolb.2021.795367
DO - 10.3389/fmolb.2021.795367
M3 - Review article
AN - SCOPUS:85120576880
VL - 8
JO - Frontiers in Molecular Biosciences
JF - Frontiers in Molecular Biosciences
SN - 2296-889X
M1 - 795367
ER -