title: High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation.
abstract: During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden ana.agostinho@ki.se.
authors.forename: Ana
authors.identifier: 0000-0001-6270-7384
authors.initials: A
authors.lastname: Agostinho
authors.affiliation: Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, Solna, Sweden.
authors.forename: Otto
authors.initials: O
authors.lastname: Manneberg
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Robin
authors.initials: R
authors.lastname: van Schendel
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Abrahan
authors.initials: A
authors.lastname: Hernández-Hernández
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Kouznetsova
authors.affiliation: Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, Solna, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Blom
authors.affiliation: Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, Solna, Sweden.
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Brismar
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Höög
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002842:Chromatids / Q000235:genetics* / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D012854:Sister Chromatid Exchange; D013090:Spermatocytes / Q000378:metabolism; D013573:Synaptonemal Complex; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D010750:Phosphoproteins; D021122:Protein Subunits; D000097722:Cohesins; C465863:Rec8 protein, mouse
keywords: cohesin; meiosis; sister chromatid cohesion; super‐resolution microscopy; synaptonemal complex