Journal
CELL CYCLE
Volume 21, Issue 5, Pages 501-513Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2021.2023304
Keywords
Roberts syndrome (RBS); cornelia de lange syndrome (Cdls); cohesinopathies; thalidomide; birth defects; CRL4 ubiquitin ligase
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Funding
- Lehigh University [Nemes Graduate Student Research Fellowship]
- Lehigh University
- National Institutes of Health [R15GM110631]
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This study identified a unifying mechanism that links Cornelia de Lange syndrome and Roberts syndrome to thalidomide-induced teratogenicity. It showed that Esco2 and cohesin co-regulate the transcription of a component of CRL4 ubiquitin ligase, which is the pathway through which thalidomide exerts its teratogenic effects.
Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) are severe developmental maladies that arise from mutation of cohesin (including SMC3, CdLS) and ESCO2 (RBS). Though ESCO2 activates cohesin, CdLS and RBS etiologies are currently considered non-synonymous and for which pharmacological treatments are unavailable. Here, we identify a unifying mechanism that integrates these genetic maladies to pharmacologically-induced teratogenicity via thalidomide. Our results reveal that Esco2 and cohesin co-regulate the transcription of a component of CRL4 ubiquitin ligase through which thalidomide exerts teratogenic effects. These findings are the first to link RBS and CdLS to thalidomide teratogenicity and offer new insights into treatments.
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