Abstract
Compared to most common posttranslational modifications of proteins, a peculiarity of poly(ADP-ribosyl)ation is the molecular heterogeneity and complexity of the reaction product, poly(ADP-ribose) (PAR). In fact, protein-bound PAR consists of variously sized (2–200 ADP-ribose residues) linear or branched molecules, negatively charged at physiological pH. It is now clear that PAR not only affects the function of the polypeptide to which it is covalently bound, but it can also influence the activity of other proteins by engaging specific noncovalent interactions. In the last 10 years, the family of PAR-binding proteins has been rapidly growing and functional studies have expanded the regulatory potential of noncovalent protein targeting by PAR far beyond initial assumptions.
In this chapter, methods are described for: (1) PAR synthesis and analysis; (2) detecting PAR-binding proteins in protein mixtures; (3) defining affinity and specificity of PAR binding to individual proteins or protein fragments; and (4) identifying PAR molecules selectively involved in the interaction.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Amé J-C, Spenlehauer C, de Murcia G (2004) The PARP superfamily. Bioessays 26:882–893
Okano S, Lan L, Caldecott KW, Mori T, Yasui A (2003) Spatial and temporal cellular responses to single-strand breaks in human cells. Mol Cell Biol 23:3974–3981
Haince J-F, McDonald D, Rodrigue A, Déry U, Masson J-Y, Hendzel MJ, Poirier GG (2008) PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites. J Biol Chem 283:1197–1208
Malanga M, Althaus FR (2005) The role of poly(ADP-ribose) in the DNA damage signalling network. Biochem Cell Biol 83:354–364
Reale A, De Matteis G, Galleazzi G, Zampieri M, Caiafa P (2005) Modulation of DNMT1 activity by ADP-ribose polymers. Oncogene 24:13–19
Ahel I, Ahel D, Matsusaka T, Clark AJ, Pines J, Boulton SJ, West SC (2008) Poly(DP-ribose)-binding zinc finger motifs in DNA repair/checkpoint proteins. Nature 451:81–85
Malanga M, Czubaty A, Girstun A, Staron K, Althaus FR (2008) Poly(ADP-ribose) binds to the splicing factor ASF/SF2 and regulates its phosphorylation by DNA topoisomerase I. J Biol Chem 18:19991–19998
Ji YA, Tulin AV (2009) Poly(ADP-ribosyl)ation of heterogeneous nuclear ribonucleoproteins modulates splicing. Nucleic Acids Res 37:3501–3513
Ahel D, Horejsi Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, West SC, Jackson SP, Owen-Hughes T, Boulton SJ (2009) Poly(ADP-ribose) dependent regulation of DNA repair by the chromatin remodelling enzyme ALC1. Science 325:1240–1243
Timinszky G, Till S, Hassa PO, Hothorn M, Kustatscher G, Nijmeijer B, Colombelli J, Altmeyer M, Stelzer EHK, Scheffzek K, Hottiger MO, Ladurner A (2009) A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation. Nat Struct Mol Biol 16:923–929
Masson M, Niedergang C, Schreiber V, Muller S, Menissier-de Murcia J, de Murcia G (1998) XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol Cell Biol 18:3562–3571
Panzeter PL, Realini C, Althaus FR (1992) Noncovalent interactions of poly(adenosine diphosphate ribose) with histones. Biochemistry 31:1379–1385
Malanga M, Atorino L, Tramontano F, Farina B, Quesada P (1998) Poly(ADP-ribose) binding properties of histone H1 variants. Biochim Biophys Acta 1399:154–160
Fahrer J, Kranaster R, Altmeyer M, Marx A, Buerkle A (2007) Quantitative analysis of the binding affinity of poly(ADP-ribose) to specific binding proteins as a function of chain length. Nucleic Acids Res 35:e143
Fahrer J, Popp O, Malanga M, Beneke S, Markovitz DM, Ferrando-May E, Buerkle A, Kappes F (2010) High affinity interaction of poly(ADP-ribose) and the human DEK oncoprotein depends upon chain length. Biochemistry 49:7119–7130
Pleschke JM, Kleczkowska HE, Strom M, Althaus FR (2000) Poly(ADP-ribose) binds to specific domains in DNA damage checkpoint proteins. J Biol Chem 275:40974–40980
Gagné JP, Hunter JM, Labreque B, Chabot B, Poirier GG (2003) A proteomic approach to the identification of heterogeneous nuclear ribonucleoproteins as a new family of poly(ADP-ribose)-binding proteins. Biochem J 371:331–340
Malanga M, Pleschke JM, Kleczkowska HE, Althaus FR (1998) Poly(ADP-ribose) binds to specific domains of p53 and alters its DNA binding functions. J Biol Chem 273 :11839–11843
Gagné J-P, Maxime I, Lo KS, Bourassa S, Hendzel MJ, Dawson V, Dawson TM, Poirier GG (2008) Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes. Nucleic Acids Res 36:6959–6976
Karras GI, Kustatscher G, Bubecha HR, Allen MD, Pugieux C, Sait F, Bycroft M, Ladurner AG (2005) The macro domain is an ADP-ribose binding module. EMBO J 24:1911–1920
Panzeter PL, Zweifel B, Malanga M, Waser SH, Richard M-C, Althaus FR (1993) Targeting of histone tails by poly(ADP-ribose). J Biol Chem 268:17662–17664
Panzeter PL, Althaus FR (1990) High resolution size analysis of ADP-ribose polymers using modified DNA sequencing gels. Nucleic Acids Res 18:2194
Panzeter PL, Zweifel B, Althaus FR (1992) The α-glicosidic bond of poly(ADP-ribose) are acid-labile. Biochem Biophys Res Commun 184:544–548
Malanga M, Farina B (2000) Noncovalent binding of poly(ADP-ribose) to nuclear matrix proteins: developmental changes and tissue specificity. Biol Chem 381:1047–1053
Acknowledgments
The author’s work has been supported by the Swiss National Science Foundation and the Italian Ministry for University and Research.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Malanga, M., Althaus, F.R. (2011). Noncovalent Protein Interaction with Poly(ADP-Ribose). In: Tulin, A. (eds) Poly(ADP-ribose) Polymerase. Methods in Molecular Biology, vol 780. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-270-0_5
Download citation
DOI: https://doi.org/10.1007/978-1-61779-270-0_5
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-269-4
Online ISBN: 978-1-61779-270-0
eBook Packages: Springer Protocols