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., Jakob, B., Cherry, Amy ORCID: https://orcid.org/0000-0002-8222-1071, Gueven, N., Fusser, M., Kijas, A.W., Peng, C., Katyal, S., McKinnon, P.J., Chen, J., Epe, B., Smerdon, S.J., 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

[thumbnail of Nucl. Acids Res.-2010-Becherel-1489-503.pdf]
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 Discrete Keywords: genome integrity, repair and replication
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: College of Health, Life and Environmental Sciences > School of Science and the Environment
Related URLs:
Copyright Info: Open Access article
Depositing User: Amy Cherry
Date Deposited: 30 Sep 2013 16:21
Last Modified: 24 Sep 2022 04:00
URI: https://worc-9.eprints-hosting.org/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.