RNF4‐Dependent Hybrid SUMO‐Ubiquitin Chains are Signals for RAP80 and thereby Mediate the Recruitment of BRCA1 to Sites of DNA Damage
| Autor: | Jianmei Zhu, Christopher E. Berndsen, Ajit B. Datta, Roger A. Greenberg, Catherine M. Guzzo, Cynthia Wolberger, Michael J. Matunis, Vibhor Gupta |
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| Rok vydání: | 2013 |
| Předmět: |
DNA Repair
DNA damage DNA repair Ubiquitin-Protein Ligases cells Amino Acid Motifs SUMO-1 Protein genetic processes SUMO protein environment and public health Biochemistry Article DDB1 chemistry.chemical_compound Ubiquitin Cell Line Tumor Genetics Humans DNA Breaks Double-Stranded Histone Chaperones Protein–DNA interaction Ubiquitins Replication protein A Molecular Biology chemistry.chemical_classification DNA ligase biology BRCA1 Protein Chemistry RNF4 Nuclear Proteins Sumoylation Cell Biology DNA repair protein XRCC4 Ubiquitin ligase Cell biology DNA-Binding Proteins enzymes and coenzymes (carbohydrates) health occupations biology.protein Carrier Proteins DNA Function (biology) Transcription Factors Biotechnology |
| Zdroj: | The FASEB Journal. 27 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fasebj.27.1_supplement.782.7 |
| Popis: | The DNA repair function of the breast cancer susceptibility protein BRCA1 depends in part on its interaction with RAP80, which targets BRCA1 to DNA double strand breaks (DSBs) through recognition of K63-linked polyubiquitin chains. The localization of BRCA1 to DSBs also requires sumoylation. Here, we demonstrated that, in addition to having ubiquitin-interacting motifs, RAP80 also contains a SUMO-interacting motif (SIM) that is critical for recruitment to DSBs. In combination with the ubiquitin-binding activity of RAP80, this SIM enabled RAP80 to bind with nanomolar affinity to hybrid chains consisting of ubiquitin conjugated to SUMO. Furthermore, RNF4, a SUMO-targeted ubiquitin E3 ligase that synthesizes hybrid SUMO-ubiquitin chains, localized to DSBs and was critical for the recruitment of RAP80 and BRCA1 to sites of DNA damage. Our findings, therefore, connect ubiquitin-dependent and SUMO-dependent DSB recognition, revealing that RNF4 synthesized hybrid SUMO-ubiquitin chains are recognized by RAP80 to promote BRCA1 recruitment and DNA repair. |
| Databáze: | OpenAIRE |
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