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PLoS Genet. 2013;9(12):e1004036. doi: 10.1371/journal.pgen.1004036. Epub 2013 Dec 19.

Cohesinopathies of a feather flock together.

Author information

1
Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America.
2
Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America ; Merck, Sharp & Dohme, West Point, Pennsylvania, United States of America.
3
Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America ; Janssen R&D, LLC, Raritan, New Jersey, United States of America.

Abstract

Roberts Syndrome (RBS) and Cornelia de Lange Syndrome (CdLS) are severe developmental maladies that present with nearly an identical suite of multi-spectrum birth defects. Not surprisingly, RBS and CdLS arise from mutations within a single pathway--here involving cohesion. Sister chromatid tethering reactions that comprise cohesion are required for high fidelity chromosome segregation, but cohesin tethers also regulate gene transcription, promote DNA repair, and impact DNA replication. Currently, RBS is thought to arise from elevated levels of apoptosis, mitotic failure, and limited progenitor cell proliferation, while CdLS is thought to arise, instead, from transcription dysregulation. Here, we review new information that implicates RBS gene mutations in altered transcription profiles. We propose that cohesin-dependent transcription dysregulation may extend to other developmental maladies; the diagnoses of which are complicated through multi-functional proteins that manifest a sliding scale of diverse and severe phenotypes. We further review evidence that cohesinopathies are more common than currently posited.

PMID:
24367282
PMCID:
PMC3868590
DOI:
10.1371/journal.pgen.1004036
[Indexed for MEDLINE]
Free PMC Article

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