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Title: Diffusion and distal linkages govern interchromosomal dynamics during meiotic prophase
The pairing of homologous chromosomes (homologs) in meiosis is essential for distributing the correct numbers of chromosomes into haploid gametes. 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. 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. 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. 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. 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. 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.  more » « less
Award ID(s):
2102726
PAR ID:
10354193
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
119
Issue:
12
ISSN:
0027-8424
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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