Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2.

Oliver, A W, Amé, J C, Roe, S M, Good, V, de Murcia, G and Pearl, L H (2004) Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2. Nucleic Acids Research, 32 (2). pp. 456-464. ISSN 0305-1048

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Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Antony Oliver
Date Deposited: 06 Feb 2012 20:50
Last Modified: 07 Mar 2017 05:30
URI: http://sro.sussex.ac.uk/id/eprint/28431

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