First Author | Klochendler-Yeivin A | Year | 2006 |
Journal | Mol Cell Biol | Volume | 26 |
Issue | 7 | Pages | 2661-74 |
PubMed ID | 16537910 | Mgi Jnum | J:106934 |
Mgi Id | MGI:3619788 | Doi | 10.1128/MCB.26.7.2661-2674.2006 |
Citation | Klochendler-Yeivin A, et al. (2006) Increased DNA damage sensitivity and apoptosis in cells lacking the Snf5/Ini1 subunit of the SWI/SNF chromatin remodeling complex. Mol Cell Biol 26(7):2661-74 |
abstractText | 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. |