The role of ADP-ribosylation in regulating DNA interstrand crosslink repair.

Autor:	Gunn AR; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Banos-Pinero B; Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK., Paschke P; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Sanchez-Pulido L; MRC Human Genetics Unit, The MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK., Ariza A; Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK., Day J; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Emrich M; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Leys D; Manchester Institute of Biotechnology, University of Manchester, Princess Street 131, Manchester, M1 7DN, UK., Ponting CP; MRC Human Genetics Unit, The MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK., Ahel I; Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK ivan.ahel@path.ox.ac.uk nicholas.lakin@bioch.ox.ac.uk., Lakin ND; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK ivan.ahel@path.ox.ac.uk nicholas.lakin@bioch.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2016 Oct 15; Vol. 129 (20), pp. 3845-3858. Date of Electronic Publication: 2016 Sep 01.
DOI:	10.1242/jcs.193375
Abstrakt:	ADP-ribosylation by ADP-ribosyltransferases (ARTs) has a well-established role in DNA strand break repair by promoting enrichment of repair factors at damage sites through ADP-ribose interaction domains. Here, we exploit the simple eukaryote Dictyostelium to uncover a role for ADP-ribosylation in regulating DNA interstrand crosslink repair and redundancy of this pathway with non-homologous end-joining (NHEJ). In silico searches were used to identify a protein that contains a permutated macrodomain (which we call aprataxin/APLF-and-PNKP-like protein; APL). Structural analysis reveals that this permutated macrodomain retains features associated with ADP-ribose interactions and that APL is capable of binding poly(ADP-ribose) through this macrodomain. APL is enriched in chromatin in response to cisplatin treatment, an agent that induces DNA interstrand crosslinks (ICLs). This is dependent on the macrodomain of APL and the ART Adprt2, indicating a role for ADP-ribosylation in the cellular response to cisplatin. Although adprt2 - cells are sensitive to cisplatin, ADP-ribosylation is evident in these cells owing to redundant signalling by the double-strand break (DSB)-responsive ART Adprt1a, promoting NHEJ-mediated repair. These data implicate ADP-ribosylation in DNA ICL repair and identify that NHEJ can function to resolve this form of DNA damage in the absence of Adprt2. Competing Interests: The authors declare no competing or financial interests. (© 2016. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu