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

Becherel, Olivier J., Jakob, Burkhard, Cherry, Amy L., Gueven, Nuri, Fusser, Markus, Kijas, Amanda W., Peng, Cheng, Katyal, Sachin, McKinnon, Peter J., Chen, Junjie, Epe, Bernd, Smerdon, Stephen J., Taucher-Scholz, Gisela and Lavin, Martin F. (2010) CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response. Nucleic Acids Research, 38 5: 1489-1503. doi:10.1093/nar/gkp1149

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author Becherel, Olivier J.
Jakob, Burkhard
Cherry, Amy L.
Gueven, Nuri
Fusser, Markus
Kijas, Amanda W.
Peng, Cheng
Katyal, Sachin
McKinnon, Peter J.
Chen, Junjie
Epe, Bernd
Smerdon, Stephen J.
Taucher-Scholz, Gisela
Lavin, Martin F.
Title CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response
Journal name Nucleic Acids Research   Check publisher's open access policy
ISSN 0305-1048
1362-4954
1362-4962
0261-3166
0952-3472
Publication date 2010-03
Year available 2009
Sub-type Article (original research)
DOI 10.1093/nar/gkp1149
Open Access Status DOI
Volume 38
Issue 5
Start page 1489
End page 1503
Total pages 15
Place of publication Oxford, U.K.
Publisher Oxford University Press
Collection year 2011
Language eng
Formatted 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.
© The Author(s) 2009. Published by Oxford University Press.
Keyword Strand break repair
Histidine triad superfamily
Ocular motor apraxia
Histone H2AX
FHA domain
Ataxia-telangiectasia
Polynucleotide kinase
Chromatin retention
Cellular responses
Protein aprataxin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 14 December 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 18 Apr 2010, 00:01:46 EST