TY - JOUR T1 - Homologous locus pairing is a transient, diffusion-mediated process in meiotic prophase JF - bioRxiv DO - 10.1101/2021.04.23.440859 SP - 2021.04.23.440859 AU - Trent A. C. Newman AU - Bruno Beltran AU - James M. McGehee AU - Daniel Elnatan AU - Cori K. Cahoon AU - Michael R. Paddy AU - Daniel B. Chu AU - Andrew J. Spakowitz AU - Sean M. Burgess Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/24/2021.04.23.440859.abstract N2 - The pairing of homologous chromosomes in meiosis I is essential for sexual reproduction and is mediated, in part, by the formation and repair of Spo11-induced DNA double strand breaks (DSBs). In budding yeast, each cell receives ~150-200 DSBs, yet only a fraction go on to form crossover products. How and why the cell initially co-ordinates so many interactions along each chromosome is not well understood. Using a fluorescent reporter-operator system (FROS), we measure the kinetics of interacting homologous loci at various stages of meiosis. We find that while tagged loci undergo considerable motion throughout prophase I, they are constrained in how far they can diffuse from their homolog pair. This effective tethering radius decreases over the course of meiosis in a DSB-dependent manner. We develop a theoretical model that captures the biological contributions of centromere attachment to the nuclear envelope, homolog pairing, and nuclear confinement. With this model, we demonstrate that the experimentally observed heterogeneity in single-cell behavior and the effective tethering between loci is captured for two polymers forming randomly-spaced linkages. The small number of connections required to reproduce our data demonstrates that a single linkage site between homologous chromosomes can constrain the movement of loci up to hundreds of kilobases away.Significance Statement Meiosis is essential for sexual reproduction, and homologous chromosome pairing is a critical step in this process that must be reliably achieved. We measure the dynamics of homologous loci throughout prophase I of meiosis, demonstrating the transient nature of homolog contacts and heterogeneity in single-cell behavior. We develop a minimal model containing only the basic polymer physics of DNA but is sufficient to reproduce the observed behavior. We show that it only takes a handful of homologous linkages per chromosome to facilitate pairing, demonstrating that a single tethered locus can drastically restrict the diffusion of DNA tens to hundreds of kilobases away. These results demonstrate the central role of random diffusion and polymer physics in facilitating chromosome pairing in meiosis.Competing Interest StatementThe authors have declared no competing interest. ER -