Single-Molecule Imaging Reveals Conformational Manipulation of Holliday Junction DNA by the Junction Processing Protein RuvA

Biochemistry
Dalton R Gibbs, Soma Dhakal

Abstract

Interactions between DNA and motor proteins regulate nearly all biological functions of DNA such as gene expression, DNA replication and repair, and transcription. During the late stages of homologous recombination (HR), the Escherichia coli recombination machinery, RuvABC, resolves the four-way DNA motifs called Holliday junctions (HJs) that are formed during exchange of nucleotide sequences between two homologous duplex DNA. Although the formation of the RuvA-HJ complex is known to be the first critical step in the RuvABC pathway, the mechanism for the binding interaction between RuvA and HJ has remained elusive. Here, using single-molecule fluorescence resonance energy transfer (smFRET) and ensemble analyses, we show that RuvA stably binds to the HJ, halting its conformational dynamics. Our FRET experiments in different ionic environments created by Mg2+ and Na+ ions suggest that RuvA binds to the HJ via electrostatic interaction. Further, while recent studies have indicated that the HR process can be modulated for therapeutic applications by selective targeting of the HJ by chemotherapeutic drugs, we investigated the effect of drug-modified HJ on binding. Using cisplatin as a proof-of-concept drug, we show that RuvA binds t...Continue Reading

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Citations

Jul 10, 2019·Nucleic Acids Research·Anoja MegalathanSoma Dhakal
Aug 14, 2019·Sensors·Kumar SapkotaSoma Dhakal
Jun 6, 2019·Methods and Protocols·Dalton R GibbsSoma Dhakal
Dec 11, 2019·International Journal of Molecular Sciences·Dalton R Gibbs, Soma Dhakal
Mar 16, 2021·ACS Sensors·Anoja MegalathanSoma Dhakal
Mar 22, 2021·Nucleic Acids Research·Piero R Bianco, Yue Lu
Mar 20, 2021·Biophysical Journal·Dalton R GibbsSoma Dhakal
Feb 21, 2019·ACS Sensors·Anisa KaurSoma Dhakal

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