title: Translational mechanisms at work in the cohesinopathies.
abstract: Chromosome cohesion, mediated by the cohesin complex, is essential for the process of chromosome segregation. Mutations in cohesin and its regulators are associated with a group of human diseases known as the cohesinopathies. These diseases are characterized by defects in head, face, limb, and heart development, mental retardation, and poor growth. The developmental features of the diseases are not well explained by defects in chromosome segregation, but instead are consistent with changes in gene expression during embryogenesis. Thus a central question to understanding the cohesinopathies is how mutations in cohesin lead to changes in gene expression. One of the prevailing models is that cohesin binding to promoters and enhancers directly regulates transcription. I propose that in addition cohesin may influence gene expression via translational mechanisms. If true, cohesinopathies may be related in etiology to another group of human diseases known as ribosomopathies, diseases caused by defects in ribosome biogenesis. By considering this possibility we can more fully evaluate causes and treatments for the cohesinopathies.
authors.affiliation: The Stowers Institute for Medical Research, Kansas City, MO, USA. JEG@stowers.org
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gerton
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D002875:Chromosomes / Q000378:metabolism; D019465:Craniofacial Abnormalities / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D003635:De Lange Syndrome / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D004480:Ectromelia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006972:Hypertelorism / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D014176:Protein Biosynthesis / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C492318:SMC3 protein, human; C500785:ESCO2 protein, human