Mechanisms of MLL gene rearrangement: site-specific DNA cleavage within the breakpoint cluster region is independent of chromosomal context
| Autor: | Junjie Wang, Martin Stanulla, Sheila N. Jani-Sait, Pradheepkumar P. Chhalliyil, Peter D. Aplan |
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| Rok vydání: | 2001 |
| Předmět: |
Genetic Vectors
Context (language use) Apoptosis Biology chemistry.chemical_compound Jurkat Cells Mice Plasmid hemic and lymphatic diseases Extrachromosomal DNA Proto-Oncogenes Genetics Tumor Cells Cultured Animals Humans Nuclear Matrix neoplasms Molecular Biology Genetics (clinical) Gene Rearrangement Binding Sites breakpoint cluster region Chromosome Breakage General Medicine Gene rearrangement DNA Neoplasm Histone-Lysine N-Methyltransferase Precursor Cell Lymphoblastic Leukemia-Lymphoma Molecular biology Chromatin DNA-Binding Proteins chemistry Chromosome breakage DNA Myeloid-Lymphoid Leukemia Protein Plasmids Transcription Factors |
| Zdroj: | Human molecular genetics. 10(22) |
| ISSN: | 0964-6906 |
| Popis: | The MLL gene at chromosome band 11q23 is specifically cleaved at a unique site within its breakpoint cluster region (bcr) during the higher order chromatin fragmentation associated with apoptosis. We now show that the same specific DNA cleavage event can be detected in an exogenous MLL bcr fragment that is integrated into the genome outside of its normal chromosomal context, as well as in an extrachromosomal episome containing an MLL bcr fragment. We also show that episomal or randomly integrated copies of the MLL bcr behave similar to the endogenous MLL bcr when tested in a scaffold-associated region (SAR) assay. Furthermore, an episomal murine MLL bcr introduced into human cells is cleaved at the same site as the endogenous murine MLL bcr; this episomal murine MLL bcr also functions as a SAR in human cells. We conclude that both nuclear DNA scaffold attachment as well as site-specific DNA cleavage can be directed by sequences contained within the MLL bcr, and that it is feasible to study these events using episomal shuttle vectors. |
| Databáze: | OpenAIRE |
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