BMI1 Is Recruited to DNA Breaks and Contributes to DNA Damage-Induced H2A Ubiquitination and Repair
| Autor: | Atul Kulkarni, Jay Oza, Karim Nacerddine, Ming Yao, Maarten van Lohuizen, Sarah J. Hill, Elisabetta Citterio, Shridar Ganesan, Vasudeva Ginjala |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Chromatin Immunoprecipitation
DNA Repair DNA repair DNA damage Ubiquitin-Protein Ligases Blotting Western Fluorescent Antibody Technique Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins macromolecular substances Protein Serine-Threonine Kinases Histones Proto-Oncogene Proteins Humans DNA Breaks Double-Stranded Phosphorylation RNA Small Interfering Molecular Biology Replication protein A Polycomb Repressive Complex 1 biology Histone ubiquitination Tumor Suppressor Proteins Cell Cycle Ubiquitination Nuclear Proteins Articles Cell Biology Molecular biology Proliferating cell nuclear antigen DNA-Binding Proteins Repressor Proteins Histone biology.protein DNA mismatch repair HeLa Cells Signal Transduction Nucleotide excision repair |
| Zdroj: | Molecular and Cellular Biology. 31:1972-1982 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00981-10 |
| Popis: | DNA damage activates signaling pathways that lead to modification of local chromatin and recruitment of DNA repair proteins. Multiple DNA repair proteins having ubiquitin ligase activity are recruited to sites of DNA damage, where they ubiquitinate histones and other substrates. This DNA damage-induced histone ubiquitination is thought to play a critical role in mediating the DNA damage response. We now report that the polycomb protein BMI1 is rapidly recruited to sites of DNA damage, where it persists for more than 8 h. The sustained localization of BMI1 to damage sites is dependent on intact ATM and ATR and requires H2AX phosphorylation and recruitment of RNF8. BMI1 is required for DNA damage-induced ubiquitination of histone H2A at lysine 119. Loss of BMI1 leads to impaired repair of DNA double-strand breaks by homologous recombination and the accumulation of cells in G(2)/M. These data support a crucial role for BMI1 in the cellular response to DNA damage. |
| Databáze: | OpenAIRE |
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