The kleisin subunit controls the function of meiotic cohesins by determining the mode of DNA binding and differential regulation by SCC-2 and WAPL-1

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.

DNA double‐strand breaks regulate the cleavage‐independent release of Rec8‐cohesin during yeast meiosis

“…Recently, it is shown that a DDR kinase, ATM, regulates cohesin association through the inactivation of WAPL in early prophase I in C. elegans meiosis (Z. Yu et al, 2023). And also, in C. elegans , two meiosis‐specific cohesin with REC‐8 or COH‐3/4 display distinct dynamics on the meiotic chromosome (Castellano‐Pozo et al, 2023). While REC‐8 cohesin stably binds to the chromosome, COH‐3/4 cohesin is dynamic with the association and dissociation in meiotic prophase I.…”

Two structurally mobile regions control the conformation and function of metamorphic meiotic HORMAD proteins

“…Images were acquired on a Delta vision microscope as 3D stacks using the same exposure settings between genotypes to be compared. Quantitative analysis of fluorescence intensity was performed as previously described 62 . Briefly, non-deconvolved images were analysed in Image J using a customized macro.…”