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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Clustering of Stacked Nucleobases in a Stretched DNA Conformation Enhances Facilitated Diffusion of DNA Binding Proteins as Revealed by Molecular Dynamics Simulations

DNA damage and repair refer to the creation and correction of DNA lesions that threat genome integrity. Homologous recombination is the common mechanism to prevent the DNA from the deleterious effects caused by mutations due to the error in replication or induced by environmental changes. Experiments (Chen Z. et al., 2008 and Chen J. et al., 2017) show that during the process, RecA protein binds with genomic DNA, which is unusually elongated (approximately 1.5 times to its contour length in B-DNA) and its nucleobases are clustered together in a specific manner. How these structural changes in DNA affect its interaction with the protein? What are the implications of such structural diversity in identifying damaged DNA sites? Aided by extensive Langevin dynamics simulations we probe these issues, where we study the diffusion of a protein on a force induced stretched DNA. Upon pulling systematically at the 3’ termini of a 100 bp DNA by constant forces, the DNA exhibits a conformational transition from B-DNA to ladder-like S-DNA conformation via ∑-DNA (see figure below) intermediate. Our analysis suggests that the resulting stretched DNA features non-uniform clusters of nucleotide bases such as doublets, triplets, quadruplets and so on separated by large rise gap. We found that relative population of these clusters govern the ruggedness of the protein-DNA binding energy landscape and thereby the ability of a protein to locate its target DNA sites. By analyzing different force regimes, we delineate the underlying translocation mechanism of a DNA binding protein and underscore the significance of triplex formation in regulating the protein diffusion on DNA. In my presentation, I shall describe our recent findings and discuss them in the light of recent experimental observations.

mandal-fig.gif References
    Chen Z., Yang H., Paveltich N. P. (2008). Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structures. Nature 453, 489-494.

    Chen J., Tang Q., Guo S., Lu C., Le S., Yan J. (2017). Parallel triplex structure formed between stretched single-stranded DNA and homologous duplex DNA. Nucleic Acids Res. 45, 10032-10041.

Anupam Mondal
Arnab Bhattacherjee*

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Anupam, a doctoral student in Jawaharlal Nehru University, India under Dr. Arnab Bhattacherjee will provide a short oral.

School of Computational and Integrative Sciences
Jawaharlal Nehru University
New Delhi-110067, India

Ph: (+91) 7838156636
Email: anupam68_sit@jnu.ac.in
Ph: (011) 26704787
*Email: arnab@jnu.ac.in