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Klochendler-Yeivin, A. et al.

Klochendler-Yeivin, Picarsky, Yaniv,

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

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.[1]

References

Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex. Klochendler-Yeivin, A., Picarsky, E., Yaniv, M. Mol. Cell. Biol. (2006) [Pubmed]

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