Biology subjects

Velasco Berrelleza, V. M.

Publications and source records attributed to Velasco Berrelleza, V. M..

3 recordsLinked to original sources

bioRxiv2025

Imaging and mechanism of DNA-DNA recognition mediated by divalent ions

In the cell, DNA must be tightly packed to facilitate its organisation into the nucleus, where recognition of homologous sequences underpins key processes such as recombination. Yet the structural basis of DNA-DNA pairing remains unknown. Here we combine high-resolution AFM and atomistic MD simulations to provide the first direct visualisation of DNA pairing in the presence of divalent ions. We show that strongly paired DNAs often achieve groove-to-groove alignment, driven by ionic bridges connecting the minor grooves of the two duplexes. These contacts are further stabilized by sequence-specific interactions, whose strength and specificity vary with the ion type. This mechanism of ion-mediated groove alignment provides a molecular framework for the long-hypothesized "helical alignment" model, in which homologous recognition is facilitated by preserving structural register between the two helices. Together, our findings reveal a fundamental principle by which divalent ions promote DNA-DNA pairing, with broad implications for chromosomal condensation and genome organization.

biophysics↗

bioRxiv2025

Nucleosome-mediated conformational switches in micro-eccDNAs

Extrachromosomal-circular DNA (eccDNA) are circular-DNA elements that are implicated in cellular processes such as genomic diversification and instability, along with other genomic mechanisms. However, their structure and chromatinization state is poorly understood. Here we identified a 358-bp circular micro-eccDNA molecule derived from the human Titin gene, which was selected for this study based on its size and sequence characteristics, and used atomistic molecular dynamics simulations to study its interaction with nucleosomes and corresponding topological state. We show the presence or absence of bound nucleosomes provides a topological switch between intact and denatured DNA.

biophysics↗

bioRxiv2025

TORCphysics: A physical model of DNA-topology-controlled gene expression

DNA superhelicity and transcription are intimately related because changes to DNA topology can influence gene expression and vice versa. Information is transferred through the modulation of local DNA torsional stress, where the expression of one gene may influence the superhelical level of neighbouring genes, either promoting or repressing their expression. In this work, we introduce a one-dimensional physical model that simulates supercoiling-mediated regulation. This TORCphysics model takes as input a genome architecture represented either by a plasmid or by a linear DNA sequence with ends constrained under specific biological conditions, and computes the molecules output. Our findings demonstrate that the expression profiles of genes are directly influenced by the gene circuit design, including gene location, the positions of topological barriers, promoter sequences, and topoisomerase activity. The novelty that TORCphysics offers is versatility, where users can define distinct activity models for different types of proteins and protein binding sites. The aim of this research is to establish a flexible framework for developing physical simulations of gene circuits to deepen our comprehension of the intricate mechanisms involved in gene regulation.

biophysics↗