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CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response


Becherel, OJ and Jakob, B and Cherry, AL and Guven, N and Fusser, M and Kijas, AW and Peng, C and Katyal, S and McKinnon, PJ and Chen, J and Epe, B and Smerdon, SJ and Taucher-Scholz, G and Lavin, MF, CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response, Nucleic Acids Research pp. 1-15. ISSN 1362-4962 (2009) [Refereed Article]


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Licenced under Creative Commons Attribution-NonCommercial 2.5 Generic (CC BY-NC 2.5)

DOI: doi:10.1093/nar/gkp1149


ABSTRACT 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.

Item Details

Item Type:Refereed Article
Keywords:Aprataxin, MDC1, DNA damage response
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Signal transduction
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Guven, N (Dr Nuri Guven)
ID Code:79275
Year Published:2009
Web of Science® Times Cited:48
Deposited By:Pharmacy
Deposited On:2012-08-29
Last Modified:2012-11-05
Downloads:496 View Download Statistics

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