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

ABSTRACT: 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 approximately 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.

SUBMITTER: Revenkova E

PROVIDER: S-EPMC2722190 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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

Revenkova Ekaterina E Focarelli Maria Luisa ML Susani Lucia L Paulis Marianna M Bassi Maria Teresa MT Mannini Linda L Frattini Annalisa A Delia Domenico D Krantz Ian I Vezzoni Paolo P Jessberger Rolf R Musio Antonio A

Human molecular genetics 20081107 3

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 approximately 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 mainte ...[more]

PMID: 18996922

Dataset Information

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

Publications

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

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