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© Research
Publication : Molecular and cellular biology

Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular and cellular biology - 01 Apr 2006

Klochendler-Yeivin A, Picarsky E, Yaniv M

Link to Pubmed [PMID] – 16537910

Mol. Cell. Biol. 2006 Apr;26(7):2661-74

The gene encoding the SNF5/Ini1 core subunit of the SWI/SNF chromatin remodeling complex is a tumor suppressor in humans and mice, with an essential role in early embryonic development. To investigate further the function of this gene, we have generated a Cre/lox-conditional mouse line. We demonstrate that Snf5 deletion in primary fibroblasts impairs cell proliferation and survival without the expected derepression of most retinoblastoma protein-controlled, E2F-responsive genes. Furthermore, Snf5-deficient cells are hypersensitive to genotoxic stress, display increased aberrant mitotic features, and accumulate phosphorylated p53, leading to elevated expression of a specific subset of p53 target genes, suggesting a role for Snf5 in the DNA damage response. p53 inactivation does not rescue the proliferation defect caused by Snf5 deficiency but reduces apoptosis and strongly accelerates tumor formation in Snf5-heterozygous mice.

http://www.ncbi.nlm.nih.gov/pubmed/16537910