Cancer-associated mutations in chromatin remodeler hSNF5 promote chromosomal instability by compromising the mitotic checkpoint
| Autor: | Robert G.J. Vries, C. Peter Verrijzer, Anton K. Raap, Lobke M.P. Zuijderduijn, Sima Kheradmand Kia, Vladimir Bezrookove, Igor Oruetxebarria, Ada Houweling |
|---|---|
| Přispěvatelé: | Biochemistry |
| Rok vydání: | 2005 |
| Předmět: |
Chromosomal Proteins
Non-Histone Fluorescent Antibody Technique Mitosis Aneuploidy Biology medicine.disease_cause Chromatin remodeling Research Communications Cell Line Polyploidy Chromosome segregation SDG 3 - Good Health and Well-being Chromosomal Instability Chromosome instability Genetics medicine Humans Genes Tumor Suppressor Transcription factor In Situ Hybridization Fluorescence Rhabdoid Tumor Mutation SMARCB1 Protein Chromatin Assembly and Disassembly medicine.disease Chromatin DNA-Binding Proteins Gene Expression Regulation Neoplastic Amino Acid Substitution Mutagenesis Cytogenetic Analysis Cancer research biological phenomena cell phenomena and immunity Signal Transduction Transcription Factors Developmental Biology |
| Zdroj: | Genes & Development, 19(6), 665-670. Cold Spring Harbor Laboratory Press |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.335805 |
| Popis: | The hSNF5 subunit of human SWI/SNF ATP-dependent chromatin remodeling complexes is a tumor suppressor that is inactivated in malignant rhabdoid tumors (MRTs). Here, we report that loss of hSNF5 function in MRT-derived cells leads to polyploidization and chromosomal instability. Re-expression of hSNF5 restored the coupling between cell cycle progression and ploidy checkpoints. In contrast, cancer-associated hSNF5 mutants harboring specific single amino acid substitutions exacerbated poly- and aneuploidization, due to abrogated chromosome segregation. We found that hSNF5 activates the mitotic checkpoint through the p16INK4a-cyclinD/CDK4-pRb-E2F pathway. These results establish that poly- and aneuploidy of tumor cells can result from mutations in a chromatin remodeler. |
| Databáze: | OpenAIRE |
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