Chemical chaperone - sorbitol corrects cohesion and translational defects in the Roberts mutant

Abstract

The cohesin protein complex plays a very important role in chromosome segregation, transcription, DNA replication and chromosome condensation. Mutations in cohesin proteins give rise to a disease collectively referred to as Cohesinopathies. The major cause of Cohesinopathies arise due to defects associated with gene expression, that give rise to developmental disorders. In this study, we have used Saccharomyces cerevisiae to mimic the Cohesinopathy disorder Roberts syndrome with mutations (eco1W216G) homologous to that of humans (esco2). Our data suggests that polyol sugars like sorbitol, can repair misfolded proteins and reduce ER and proteostatic stress. We have used sorbitol as a chemical chaperone, to check how it can restore chromosome segregation, gene expression, misregulation, protein misfolding, autophagy and translational defects in the cohesin mutant of the Roberts phenotype. In silico screening has helped us identify the possible sites on eco1, which could be possibly altering the phenotypic traits. Article HighlightsIn presence of sorbitol O_LITemperature sensitivity of the Roberts mutants is rescued. C_LIO_LIChromosome cohesion defect is reduced. C_LIO_LITranslational defects are minimized. C_LIO_LIAutophagy is enhanced C_LIO_LIMolecular docking shows its interaction with the acetyltransferase domain of ESCO2. C_LI