CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response
| Autor: | Cheng Peng, Peter J. McKinnon, Junjie Chen, G. Taucher-Scholz, Martin F. Lavin, Markus Fusser, Sachin Katyal, Olivier J. Becherel, Bernd Epe, Burkhard Jakob, Nuri Gueven, Amanda W. Kijas, Stephen J. Smerdon, A.L. Cherry |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular DNA Repair DNA repair DNA damage Molecular Sequence Data Cell Cycle Proteins Biology Genome Integrity Repair and Replication medicine.disease_cause Cell Line 03 medical and health sciences QH301 Mice Genetics medicine Animals Humans Linear Energy Transfer Protein Interaction Domains and Motifs Amino Acid Sequence Binding site Phosphorylation Casein Kinase II 030304 developmental biology Adaptor Proteins Signal Transducing Aprataxin chemistry.chemical_classification 0303 health sciences Mutation DNA ligase Binding Sites 030302 biochemistry & molecular biology Intracellular Signaling Peptides and Proteins Nuclear Proteins Molecular biology Cell biology MDC1 DNA-Binding Proteins chemistry Trans-Activators Casein kinase 2 DNA Damage |
| Zdroj: | Nucleic Acids Research Print: 0305-1048 |
| ISSN: | 1362-4962 |
| Popis: | Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1. |
| Databáze: | OpenAIRE |
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