High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation

• Published in: EMBO reports 2016-06, Vol.17 (6), p.901-913
• Main Authors: Agostinho, Ana, Manneberg, Otto, van Schendel, Robin, Hernández-Hernández, Abrahan, Kouznetsova, Anna, Blom, Hans, Brismar, Hjalmar, Höög, Christer
• Format: Article
• Language: English
• Subjects: Animals; Cell Cycle Proteins - metabolism; Cell division; Chromatids - genetics; Chromatids - metabolism; Chromatin; Chromosomal Proteins, Non-Histone - metabolism; Chromosome Segregation; Chromosomes; cohesin; Cohesins; EMBO06; Male; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; meiosis; Meiosis - genetics; Mice; Mice, Knockout; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protein Subunits - metabolism; Quantitative distribution; sister chromatid cohesion; Sister Chromatid Exchange; Spermatocytes - metabolism; super-resolution microscopy; Synaptonemal Complex
• ISSN: 1469-221X; 1469-3178; 1469-3178
• DOI: 10.15252/embr.201642030

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. Synopsis This study shows that randomly distributed but densely arranged REC8 cohesin complexes prevent local separation of sister chromatid axes and illegitimate synaptonemal complex assembly. Hypomorphic Stag3 or Smc1β −/− spermatocytes display local separation of sister chromatid axes. REC8 is absent at sites of local separation of sister chromatids where illegitimate synaptonemal complex assembly takes place. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of local separation of sister chromatids. Graphical Abstract This study shows that randomly distributed but densely arranged REC8 cohesin complexes prevent local separation of sister chromatid axes and illegitimate synaptonemal complex assembly.