An ever-changing landscape in Roberts syndrome biology: Implications for macromolecular damage.

• Main Authors: Michael G Mfarej, Robert V Skibbens
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2020-12-01
• Series: PLoS Genetics
• Online Access: https://doi.org/10.1371/journal.pgen.1009219

Roberts syndrome (RBS) is a rare developmental disorder that can include craniofacial abnormalities, limb malformations, missing digits, intellectual disabilities, stillbirth, and early mortality. The genetic basis for RBS is linked to autosomal recessive loss-of-function mutation of the establishment of cohesion (ESCO) 2 acetyltransferase. ESCO2 is an essential gene that targets the DNA-binding cohesin complex. ESCO2 acetylates alternate subunits of cohesin to orchestrate vital cellular processes that include sister chromatid cohesion, chromosome condensation, transcription, and DNA repair. Although significant advances were made over the last 20 years in our understanding of ESCO2 and cohesin biology, the molecular etiology of RBS remains ambiguous. In this review, we highlight current models of RBS and reflect on data that suggests a novel role for macromolecular damage in the molecular etiology of RBS.