How many roads lead to cohesinopathies?. Issue 11 (22nd May 2017)

• Record Type: Journal Article
• Authors: Banerji, Rajeswari; Skibbens, Robert V.; Iovine, M. Kathryn
• Other Names: Podrabsky Jason E. guestEditor.; Cornell Robert A. guestEditor.; Dorsky Richard I. guestEditor.
• Is Part Of: Developmental dynamics. Volume 246:Issue 11(2017)
• Page Start: 881
• Page End: 888
• Publication Date: 2017-05-22
• Subjects: Roberts Syndrome (RBS) -- Cornelia de Lange Syndrome (CdLS) -- DNA tethering -- cohesin -- ESCO2 -- NIPBL; Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24510
• Languages: English
• ISSNs: 1058-8388

Abstract

Abstract : Genetic mapping studies reveal that mutations in cohesion pathways are responsible for multispectrum developmental abnormalities termed cohesinopathies. These include Roberts syndrome (RBS), Cornelia de Lange Syndrome (CdLS), and Warsaw Breakage Syndrome (WABS). The cohesinopathies are characterized by overlapping phenotypes ranging from craniofacial deformities, limb defects, and mental retardation. Though these syndromes share a similar suite of phenotypes and arise due to mutations in a common cohesion pathway, the underlying mechanisms are currently believed to be distinct. Defects in mitotic failure and apoptosis i.e. trans DNA tethering events are believed to be the underlying cause of RBS, whereas the underlying cause of CdLS is largely modeled as occurring through defects in transcriptional processes i.e. cis DNA tethering events. Here, we review recent findings described primarily in zebrafish, paired with additional studies in other model systems, including human patient cells, which challenge the notion that cohesinopathies represent separate syndromes. We highlight numerous studies that illustrate the utility of zebrafish to provide novel insights into the phenotypes, genes affected and the possible mechanisms underlying cohesinopathies. We propose that transcriptional deregulation is the predominant mechanism through which cohesinopathies arise. Developmental Dynamics 246:881–888, 2017 . © 2017 Wiley Periodicals, Inc. Key Findings: Cohesion is required for bringing DNA segments together for purposes of gene regulation and for the association of sister chromatids. Cohesinopathies are diseases where one or more DNA tethering events fail. The notion that RBS and CdLS arise from distinct underlying mechanisms is challenged.