The Roles of Cohesins in Mitosis, Meiosis, and Human Health and Disease

Abstract

Summary Mitosis and meiosis are essential processes that occur during development. Throughout these processes, cohesion is required to keep the sister chromatids together until their separation at anaphase. Cohesion is created by multi-protein subunit complexes called cohesins. Although the subunits differ slightly in mitosis and meiosis, the canonical cohesin complex is composed of four subunits that are quite diverse. The cohesin complexes are also important for DNA repair, gene expression, development, and genome integrity. Here we provide an overview of the roles of cohesins during these different events, as well as their roles in human health and disease, including the cohesinopathies. Although the exact roles and mechanisms of these proteins are still being elucidated, this review will serve as a guide for the current knowledge of cohesins.

Preparation of Meiotic Chromosome Spreads from Mouse Spermatocytes

“…For example, several types of immunostaining and/or microscopy including widefield or confocal with epifluorescence, or electron can be performed. In addition to studying meiosis-specific proteins such as components of synaptonemal complex, those interacting with the SC, such as cohesins, multiprotein complexes that mediate cohesion, can be evaluated (reviewed in 10–12 ). Regulation of DNA crossover formation, processing, and maturation can be and have also been studied with this technique 13 .…”

Síndrome de Cornelia de Lange y deficiencias hormonales pituitáricas múltiples, una asociación inusual. Caso clínico.

“…Estas proteínas son importantes en la separación de cromátides antes de la mitosis, lo que explica que haya alteraciones en múltiples sistemas orgánicos. 11 Existen cinco grupos fenotípicos, uno por cada gen. 6 A pesar de esta genotipificación, el diagnóstico es, fundamentalmente, clínico.…”

Cohesin embraces new phenotypes

“…The critical role of cohesin in human development was first evidenced by the discoveries that heterozygous mutations in NIPBL and homozygous or compound heterozygous mutations in ESCO2 were responsible for CdLS and RBS, respectively 4–6 .…”

“…Whereas disturbances in cell cycle progression and DNA damage repair are observed for some individuals with CdLS, RBS and WBS, their contribution to disease pathogenesis is unclear 6 . In CdLS probands heterozygous for NIPBL mutations, cells maintain about 70% of the normal levels of NIPBL transcript and sister chromatid cohesion defects are absent 11 .…”

“…Significantly knocking down or eliminating key members of the cohesin complex is in general lethal to the organism, resulting in severe defects in chromatid segregation and aneuploidy. It was therefore surprising that mutations in components of the cohesin complex result in very specific developmental disorders in humans, collectively termed cohesinopathies, suggesting that cohesin might have roles in biological processes beyond sister chromatid segregation 4–6 .…”