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Molecular and Cellular Biology, April 2006, p. 2661-2674, Vol. 26, No. 7
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.7.2661-2674.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Increased DNA Damage Sensitivity and Apoptosis in Cells Lacking the Snf5/Ini1 Subunit of the SWI/SNF Chromatin Remodeling Complex

Agnes Klochendler-Yeivin,1* Eli Picarsky,2 and Moshe Yaniv3

Department of Animal and Cell Biology, The Institute for Life Sciences, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem 91904, Israel,1 Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel,2 Gene Expression and Disease Unit, Department of Developmental Biology, Pasteur Institute, Paris, France3

Received 6 October 2005/ Returned for modification 4 November 2005/ Accepted 5 January 2006

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.

* Corresponding author. Mailing address: Department of Animal and Cell Biology, The Institute for Life Sciences, The Hebrew University of Jerusalem, Givat-Ram, Jerusalem 91904, Israel. Phone: 00972-2-6585945. Fax: 00972-2-6585417. E-mail: agnesk{at}md.huji.ac.il.

Molecular and Cellular Biology, April 2006, p. 2661-2674, Vol. 26, No. 7
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.7.2661-2674.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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