Research

We are a molecular biophysics lab studying protein-DNA interactions in the context of transcription, reverse transcription and DNA repair, using advanced single-molecule methods rooted in the physical sciences. We develop experimental setups capable of applying mechanical forces on biological molecules and complexes, and directly measure molecular movements and conformational changes as small as Angstroms. We use these instruments to study the structure of chromatin, the interactions between transcription factors and DNA, and the machine-like function of polymerases, helicases and translocases.

 

(1) The structure and dynamics of chromatin, and its effect on transcription

S. Rudnizky, H. Khamis, Y. Ginosar, E. Goren, P. Melamed and A. Kaplan, “Extended and dynamic linker histone-DNA interactions control chromatosome compaction”, Molecular Cell (2021). PDF

S. Rudnizky*, H. Khamis*, O. Malik, P. Melamed, and A. Kaplan, “The base pair-scale diffusion of nucleosomes modulates binding of transcription factors”, PNAS doi: 10.1073/pnas.1815424116 (2019). PDF

S. Rudnizky, O. Malik, A. Bavly, L. Pnueli, P. Melamed and A. Kaplan,   “Nucleosome mobility and the regulation of gene expression: Insights from single-molecule studies“, Protein Science DOI: 10.1002/pro.3159 (2017). PDF

S. Rudnizky, A. Bavly, O. Malik, L. Pnueli, P. Melamed and A. Kaplan, “H2A.Z controls the stability and mobility of nucleosomes to regulate expression of the LH genes”, Nature Communications 7, 12958 (2016). PDF

 

(2) Interactions between transcription factors and DNA

H. Khamis, S. Rudnizky, P. Melamed and A. Kaplan, “Single molecule characterization of the binding kinetics of a transcription factor and its modulation by DNA sequence and methylation”, Nucleic Acids Research (2021). PDF

S. Rudnizky*, H. Khamis*, O. Malik, A. Squires, A. Meller, P. Melamed and A. Kaplan, “Single-molecule DNA unzipping reveals asymmetric modulation of a transcription factor by its binding site sequence and context”, Nucleic Acids Research (2017). PDF

 

 

(3) The retroviral reverse transcriptase, and its its interplay with the template’s secondary structure

O. Malik*, H. Khamis*, S. Rudnizky, A. Marx and A. Kaplan, “Pausing kinetics dominates strand-displacement polymerization by Reverse Transcriptase”, Nucleic Acids Research 45, 10190 (2017). PDF

O. Malik*, H. Khamis*, S. Rudnizky and A. Kaplan, “The mechano-chemistry of a monomeric reverse transcriptase”, Nucleic Acids Research 45, 12954 (2017). PDF

 

(4) DNA unwinding by the bacterial RecBCD helicase

V. Gaydar, R. Zananiri, L. Saied, O. Dvir, A. Kaplan and A. Henn, “Communication between DNA and nucleotide binding sites facilitates stepping by the RecBCD helicase”, Nucleic Acids Research  (2024). PDF

R. Zananiri*, S. Mangapuram Venkata*, V. Gaydar*, D. Yahalom, O. Malik, S. Rudnizky, O. Kleifeld, A. Kaplan and A. Henn, “Auxiliary ATP binding sites support DNA unwinding by RecBCD”, Nature Communications 13, 1806 (2022). PDF.

R. Zananiri, O. Malik, S. Rudnizky, V. Gaydar, R. Kreiserman, A. Henn and A. Kaplan, “Synergy between RecBCD subunits is essential for efficient DNA unwinding”, eLife 8, e40836 (2019). PDF