Cornelia de Lange Syndrome mutations in SMC1A cause cohesion defects in yeast

Abstract Cornelia de Lange Syndrome (CdLS) is a developmental disorder characterized by limb truncations, craniofacial abnormalities, and cognitive delays. CdLS is caused mainly by mutations in genes encoding subunits or regulators of the cohesin complex. Cohesin plays 2 distinct roles in chromosome dynamics as follows: it promotes looping, organization, and compaction of individual chromosomes, and it holds newly replicated sister chromatids together until cell division. CdLS-associated mutations result in altered gene expression likely by affecting chromosome architecture. Whether CdLS mutations cause phenotypes through impact on sister chromatid cohesion is less clear. Here, we show that CdLS-associated mutations introduced into the SMC1A gene of budding yeast had measurable impacts on sister chromatid cohesion, mitotic progression, and DNA damage sensitivity. These data suggest that sister chromatid cohesion-related defects may contribute to phenotypes seen in CdLS affected individuals. Mutations in the chromosome cohesion apparatus lead to developmental disorders called cohesinopathies, which have been attributed to changes in transcription. Here, Chen et al. exploit sensitive assays in budding yeast to assess the impacts of disease-associated mutations in the highly conserved cohesin subunit SMC1 on chromosome segregation and cell cycle progression. Their data suggests that some of the phenotypes in Cornelia de Lange Syndrome—a cohesinopathy—might also be attributable to cell cycle defects due to compromised sister chromatid cohesion.