In this section
@article{Haimov:2026:10.1103/n5cv-svz2,
author = {Haimov, E and Hedley, JG and Simonowicz, NE and Xiao, Y and Stannard, A and Oshanin, G and Rosa, A and Elani, Y and Kornyshev, AA},
doi = {10.1103/n5cv-svz2},
journal = {Prx Life},
title = {Recognition in Confinement: The Dynamics of Homologous Gene Pairing},
url = {http://dx.doi.org/10.1103/n5cv-svz2},
volume = {4},
year = {2026}
}
TY - JOUR
AB - How can protein-independent, side-by-side alignment of homologous double-stranded DNA (dsDNA) arise as an early step in genome repair and genetic exchange, and what determines their kinetics under confinement? Although recombination proteins are known to facilitate this process, experiments indicate that an initial side-by-side arrangement of homologs can occur even in their absence. Helical Coherence Theory (HCT) proposes that sequence-dependent distortions of the double helix lead to commensurate charge patterns between interacting dsDNAs, favoring homologous over nonhomologous alignment. However, HCT has largely been developed for straight, rigid dsDNA rods, an approximation limited to roughly one persistence length (<inf>B</inf>≈ 50 nm), leaving the question open as to how recognition manifests in longer, fluctuating chains. Moreover, the dynamics and timescales of homolog searching under confinement, and the internal dynamics of the pair ed state, such as transient formation of local unpaired regions (“bubbles”) and end fraying, remain unexplored. Here we extend HCT to dsDNA chains of multiple persistence lengths under confinement using coarse-grained simulations with a custom HCT-based force field to promote our understanding of how homologous genes pair in vivo. We simulate two homologous chains in spherical cavities spanning 0.3 to 1 times the free-space gyration radius under two limiting ionic conditions, and use the ratio of confinement radius to free-space gyration radius as a control parameter. Pairing occurs on microsecond timescales, with intermediate confinement giving the most favorable balance between rapid encounter and avoidance of kinetically trapped states. This behavior reflects a crossover from diffusion-limited search under weak confinement to trapping-dominated dynamics under strong confinement. To resolve pairing dynamics, we develop and fit a kinetic theory to simulation trajectories, distinguishing rates of
AU - Haimov,E
AU - Hedley,JG
AU - Simonowicz,NE
AU - Xiao,Y
AU - Stannard,A
AU - Oshanin,G
AU - Rosa,A
AU - Elani,Y
AU - Kornyshev,AA
DO - 10.1103/n5cv-svz2
PY - 2026///
TI - Recognition in Confinement: The Dynamics of Homologous Gene Pairing
T2 - Prx Life
UR - http://dx.doi.org/10.1103/n5cv-svz2
VL - 4
ER -
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