Biology subjects

Bisht, S.

Publications and source records attributed to Bisht, S..

4 recordsLinked to original sources

bioRxiv2025

A Causal Role for the Hippocampus in Gating Rapid Motor Memory Consolidation

How humans acquire motor skills is a fundamental biological question. Early learning involves rapid gains during practice and brief rest, yet the causal contribution of the hippocampus remains unclear. Here, we applied individualized, MRI-guided transcranial ultrasound stimulation (TUS) to modulate the posterior hippocampus in healthy adults. To establish a physiological benchmark, we first showed that this TUS protocol produced a sustained reduction in corticospinal excitability when applied to the primary motor cortex. When applied to the posterior hippocampus, electroencephalography revealed reduced frontocentral gamma-band activity, providing physiological evidence of hippocampal-frontal network modulation. Behaviorally, TUS altered the temporal dynamics of skill acquisition. Compared with sham, hippocampal TUS attenuated micro-offline gains during rest while increasing performance improvements during active practice. This shift from offline to online learning was replicated in an independent cohort with comparable baseline motor performance. Importantly, hippocampal TUS enhanced overall performance during learning, and this higher level of performance remained evident 24 hours later. Together, these findings provide causal evidence that the human hippocampus contributes to how motor learning is distributed between active practice and brief rest, showing that this temporal organization of learning can be altered by non-invasive neuromodulation.

neuroscience↗

bioRxiv2021

Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy

The condensin protein complex compacts chromatin during mitosis using its DNA-loop extrusion activity. Previous studies proposed scrunching and loop-capture models as molecular mechanisms for the loop extrusion process, both of which assume the binding of double-strand (ds) DNA to the so-called hinge domain formed at the interface of the condensin subunits Smc2 and Smc4. However, how the hinge domain contacts dsDNA has remained unknown, potentially due to its conformational plasticity. Here, we conducted atomic force microscopy imaging of the budding yeast condensin holo-complex and used this data as basis for coarse-grained molecular dynamics simulations to model the hinge structure in a transient open conformation. We then simulated the dsDNA binding to open and closed hinge conformations, predicting that dsDNA binds to the outside surface when closed and to the outside and inside surfaces when open. Our simulations also suggested that the hinge can close around dsDNA bound to the inside surface. The conformational change of the hinge domain might be essential for the dsDNA binding regulation and play important roles in condensin-mediated DNA-loop extrusion.

biophysics↗

bioRxiv2017

Real-time detection of condensin-driven DNA compaction reveals a multistep binding mechanism

Condensin, a conserved member of the SMC protein family of ring-shaped multi-subunit protein complexes, is essential for structuring and compacting chromosomes. Despite its key role, its molecular mechanism has remained largely unknown. Here, we employ single-molecule magnetic tweezers to measure, in real-time, the compaction of individual DNA molecules by the budding yeast condensin complex. We show that compaction proceeds in large (~200nm) steps, driving DNA molecules into a fully condensed state against forces of up to 2pN. Compaction can be reversed by applying high forces or adding buffer of high ionic strength. While condensin can stably bind DNA in the absence of ATP, ATP hydrolysis by the SMC subunits is required for rendering the association salt-insensitive and for subsequent compaction. Our results indicate that the condensin reaction cycle involves two distinct steps, where condensin first binds DNA through electrostatic interactions before using ATP hydrolysis to encircle the DNA topologically within its ring structure, which initiates DNA compaction. The finding that both binding modes are essential for its DNA compaction activity has important implications for understanding the mechanism of chromosome compaction.

biophysics↗

bioRxiv2017

The Condensin Complex Is A Mechanochemical Motor That Translocates Along DNA

One Sentence SummarySingle-molecule imaging reveals that eukaryotic condensin is a highly processive DNA-translocating motor complex.\n\nAbstractCondensin plays crucial roles in chromosome organization and compaction, but the mechanistic basis for its functions remains obscure. Here, we use single-molecule imaging to demonstrate that Saccharomyces cerevisiae condensin is a molecular motor capable of ATP hydrolysis-dependent translocation along double-stranded DNA. Condensins translocation activity is rapid and highly processive, with individual complexes traveling an average distance of [≥]10 kilobases at a velocity of [~]60 base pairs per second. Our results suggest that condensin may take steps comparable in length to its [~]50-nanometer coiled-coil subunits, suggestive of a translocation mechanism that is distinct from any reported DNA motor protein. The finding that condensin is a mechanochemical motor has important implications for understanding the mechanisms of chromosome organization and condensation.

biophysics↗