Cornelia de Lange syndrome mutations in SMC1A or SMC3 affect binding to DNA

Ekaterina Revenkova, Maria Luisa Focarelli, Lucia Susani, Marianna Paulis, Maria Teresa Bassi, Linda Mannini, Annalisa Frattini, Domenico Delia, Ian Krantz, Paolo Vezzoni, Rolf Jessberger, Antonio Musio

Research output: Contribution to journalArticlepeer-review


Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous developmental disorder characterized by facial dysmorphia, upper limb malformations, growth and cognitive retardation. Mutations in the sister chromatid cohesion factor genes NIPBL, SMC1A and SMC3 are present in ∼65% of CdLS patients. In addition to their canonical roles in chromosome segregation, the cohesin proteins are involved in other biological processes such as regulation of gene expression, DNA repair and maintenance of genome stability. To gain insights into the molecular basis of CdLS, we analyzed the affinity of mutated SMC1A and SMC3 hinge domains for DNA. Mutated hinge dimers bind DNA with higher affinity than wild-type proteins. SMC1A- and SMC3-mutated CdLS cell lines display genomic instability and sensitivity to ionizing radiation and interstrand crosslinking agents. We propose that SMC1A and SMC3 CdLS mutations affect the dynamic association between SMC proteins and DNA, providing new clues to the underlying molecular cause of CdLS.

Original languageEnglish
Pages (from-to)418-427
Number of pages10
JournalHuman Molecular Genetics
Issue number3
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology


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