![]() ![]() Following transfer to sporulation media, the meiotic program begins with cells entering S phase, over which time the centromeres are dispersed and telomeres start to cluster in the bouquet ( 59– 61, 74, 115). At T 0, cells are in the G0 stage prior to DNA replication, and chromosomes are arranged in the Rabl configuration with centromeres clustered at the nuclear periphery ( 59). Overview of chromosome conformations in premeiotic cells ( T M = T 0) and in meiotic cells in midprophase ( ∼ T 3, T 4) and late prophase ( ∼ T 5, T 6). Several theoretical models of pairing in yeast have been developed that take into account chromosome size, linkage numbers, and the attachment and motion of telomeres at the nuclear envelope ( 12– 16), yet no study to date has combined biophysical modeling together with empirical measurements of meiotic “pairing” dynamics in live cells.įig. ![]() These include the transition from the Rabl (centromeres-clustered) to bouquet (telomeres-clustered) configurations telomere-led chromosome movement driven by cytoskeletal motor proteins via the linker of nucleoskeleton and cytoskeleton complex the formation and repair of Spo11-induced DNA double-strand breaks (DSBs) and the assembly and disassembly of the synaptonemal complex (SC), which is a ribbon-like structure that joins homologs together along their lengths ( Fig. 1) ( 5– 11). The budding yeast, Saccharomyces cerevisiae, is an important model for the study of homolog pairing as it has been used extensively for characterizing many of the other dynamic events that occur over the course of meiotic prophase I that are now known to be conserved across phyla. These insights into the dynamic interchromosomal behavior displayed during homolog pairing demonstrate the power of combining time-resolved in vivo analysis with modeling at the granular level. The predicted number of linkages per chromosome in our theoretical model closely approximates the small number (approximately two to four) of estimated synapsis-initiation sites, suggesting that excess DSBs have negligible effects on the overall juxtaposition of homologs. The observed plateaus of the mean-square change in distance (MSCD) between foci informed the development of a biophysical model of two diffusing polymers that captures the loss of centromere linkages as cells enter meiosis, nuclear confinement, and the formation of Spo11-dependent linkages. Continuous imaging revealed highly heterogeneous cell-to-cell behavior of foci, with the majority of cells exhibiting a “mixed” phenotype where foci move into and out of proximity, even at late stages of prophase, suggesting that the axial structures of the synaptonemal complex may be more dynamic than anticipated. Having established a system to measure the position of fluorescently tagged chromosomal loci in three-dimensional space over time, we analyzed locus trajectories to determine how frequently and how long loci spend colocalized or apart. In budding yeast, pairing depends on the formation of 150 to 200 Spo11-mediated double-strand breaks (DSBs) that are distributed among 16 homolog pairs, but it is not known if all, or only a subset, of these DSBs contribute to the close juxtaposition of homologs. ![]() The pairing of homologous chromosomes (homologs) in meiosis is essential for distributing the correct numbers of chromosomes into haploid gametes. ![]()
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