University of Worcester Worcester Research and Publications
 
  USER PANEL:
  ABOUT THE COLLECTION:
  CONTACT DETAILS:

CK2 Phosphorylation-dependent Interaction Between Aprataxin and MDC1 in the DNA Damage Response.

Becherel, O.J. and Jakob, B. and Cherry, Amy and Gueven, N. and Fusser, M. and Kijas, A.W. and Peng, C. and Katyal, S. and McKinnon, P.J. and Chen, J. and Epe, B. and Smerdon, S.J. and Taucher-Scholz, G. and Lavin, M.F. (2010) CK2 Phosphorylation-dependent Interaction Between Aprataxin and MDC1 in the DNA Damage Response. Nucleic Acids Research, 38 (5). pp. 1489-1503. ISSN Print: 0305-1048 Online: 1362-4962

[img]
Preview
Text
Nucl. Acids Res.-2010-Becherel-1489-503.pdf - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (7MB) | Preview

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 Type: Article
Uncontrolled Keywords: genome integrity, repair and replication
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Academic Departments > Institute of Science and the Environment
Related URLs:
Copyright Info: Creative Commons Attribution Non-Commercial License
Depositing User: Amy Cherry
Date Deposited: 30 Sep 2013 16:21
Last Modified: 11 Dec 2014 15:25
URI: https://eprints.worc.ac.uk/id/eprint/2417

Actions (login required)

View Item View Item
 
     
Worcester Research and Publications is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.