The kleisin subunit controls the function of C. elegans meiotic cohesins by determining the mode of DNA binding and differential regulation by SCC-2 and WAPL-1
- MRC London Institute of Medical Sciences, United Kingdom
- Universidad Autónoma de Madrid, Spain
Abstract
The cohesin complex plays essential roles in chromosome segregation, 3D genome organisation, and DNA damage repair through its ability to modify DNA topology. In higher eukaryotes, meiotic chromosome function, and therefore fertility, requires cohesin complexes containing meiosis-specific kleisin subunits: REC8 and RAD21L in mammals and REC-8 and COH-3/4 in C. elegans. How these complexes perform the multiple functions of cohesin during meiosis and whether this involves different modes of DNA binding or dynamic association with chromosomes is poorly understood. Combining time-resolved methods of protein removal with live imaging and exploiting the temporospatial organisation of the C. elegans germline, we show that REC-8 complexes provide sister chromatid cohesion (SCC) and DNA repair, while COH-3/4 complexes control higher-order chromosome structure. High-abundance COH-3/4 complexes associate dynamically with individual chromatids in a manner dependent on cohesin loading (SCC-2) and removal (WAPL-1) factors. In contrast, low-abundance REC-8 complexes associate stably with chromosomes, tethering sister chromatids from S-phase until the meiotic divisions. Our results reveal that kleisin identity determines the function of meiotic cohesin by controlling the mode and regulation of cohesin-DNA association, and are consistent with a model in which SCC and DNA looping are performed by variant cohesin complexes that coexist on chromosomes.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files; source data for all graphs on the manuscript are provided in source data files associated with each figure containing graphs
Article and author information
Author details
Pablo Lopez-Jimenez
Enrique Martinez-Perez
Funding
Medical Research Council (MC-A652-5PY60)
- Enrique Martinez-Perez
European Molecular Biology Organization (Postdoctoral Fellowship)
- Maikel Castellano-Pozo
Fundacion Alfonso Martin Escudero (Postdoctoral Fellowship)
- Maikel Castellano-Pozo
European Molecular Biology Organization (Scientific exchange grant)
- Pablo Lopez-Jimenez
Universidad Autonoma de Madrid
- Jesus Page
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2023, Castellano-Pozo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The kleisin subunit controls the function of C. elegans meiotic cohesins by determining the mode of DNA binding and differential regulation by SCC-2 and WAPL-1
eLife 12:e84138.
https://doi.org/10.7554/eLife.84138
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