title: Cohesinopathies of a feather flock together.
abstract: Roberts Syndrome (RBS) and Cornelia de Lange Syndrome (CdLS) are severe developmental maladies that present with nearly an identical suite of multi-spectrum birth defects. Not surprisingly, RBS and CdLS arise from mutations within a single pathway--here involving cohesion. Sister chromatid tethering reactions that comprise cohesion are required for high fidelity chromosome segregation, but cohesin tethers also regulate gene transcription, promote DNA repair, and impact DNA replication. Currently, RBS is thought to arise from elevated levels of apoptosis, mitotic failure, and limited progenitor cell proliferation, while CdLS is thought to arise, instead, from transcription dysregulation. Here, we review new information that implicates RBS gene mutations in altered transcription profiles. We propose that cohesin-dependent transcription dysregulation may extend to other developmental maladies; the diagnoses of which are complicated through multi-functional proteins that manifest a sliding scale of diverse and severe phenotypes. We further review evidence that cohesinopathies are more common than currently posited.
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Skibbens
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Colquhoun
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America ; Merck, Sharp & Dohme, West Point, Pennsylvania, United States of America.
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Green
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: Cody A
authors.initials: CA
authors.lastname: Molnar
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Sin
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Sullivan
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America ; Janssen R&D, LLC, Raritan, New Jersey, United States of America.
authors.forename: Eden E
authors.initials: EE
authors.lastname: Tanzosh
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D003635:De Lange Syndrome / Q000235:genetics* / Q000473:pathology; D004480:Ectromelia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D006972:Hypertelorism / Q000235:genetics* / Q000473:pathology; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009154:Mutation; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins