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

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posted on 2023-06-08, 08:02 authored by Antony OliverAntony Oliver, J C Amé, S M Roe, V Good, G de Murcia, Laurence PearlLaurence Pearl
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Nucleic Acids Research

ISSN

0305-1048

Publisher

Oxford University Press

Issue

2

Volume

32

Page range

456-464

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

First Open Access (FOA) Date

2016-03-22

First Compliant Deposit (FCD) Date

2016-11-10

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