University of Worcester Worcester Research and Publications

Versatility in Phospho-dependent Molecular Recognition of the XRCC1 and XRCC4 DNA-damage Scaffolds by Aprataxin-family FHA Domains

Cherry, Amy ORCID:, Nott, T.J., Kelly, G., Rulten, S.L., Caldecott, K.W. and Smerdon, S.J. (2015) Versatility in Phospho-dependent Molecular Recognition of the XRCC1 and XRCC4 DNA-damage Scaffolds by Aprataxin-family FHA Domains. DNA Repair, 35. pp. 116-125. ISSN Print: 1568-7864 Online: 1568-7856

Cherry_et_al_2015_DNA_Repair.pdf - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview


Aprataxin, aprataxin and PNKP-like factor (APLF) and polynucleotide kinase phosphatase (PNKP) are key DNA-repair proteins with diverse functions but which all contain a homologous forkhead-associated (FHA) domain. Their primary binding targets are casein kinase 2-phosphorylated forms of the XRCC1 and XRCC4 scaffold molecules which respectively coordinate single-stranded and double-stranded DNA break repair pathways. Here, we present the high-resolution X-ray structure of a complex of phosphorylated XRCC4 with APLF, the most divergent of the three FHA domain family members. This, combined with NMR and biochemical analysis of aprataxin and APLF binding to singly and multiply-phosphorylated forms of XRCC1 and XRCC4, and comparison with PNKP reveals a pattern of distinct but overlapping binding specificities that are differentially modulated by multi-site phosphorylation. Together, our data illuminate important differences between activities of the three phospho-binding domains, in spite of a close evolutionary relationship between them.

Item Type: Article
Additional Information:

© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.

The full-text of the online published article can be accessed via the Official URL.

Uncontrolled Discrete Keywords: DNA repair, FHA domain, Aprataxin, APLF, XRCC1, XRCC4
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 journal article
Depositing User: Amy Cherry
Date Deposited: 04 Feb 2016 12:00
Last Modified: 24 Sep 2022 04:00

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.