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Role of Poly-ADP-Ribosylation in Cancer Development

This chapter appears in the following book:

Poly(ADP-Ribosyl)ation

Edited by: Alexander Burkle
ISBN: 0-387-33371-1
» Get more information about this book at landesbioscience.com «

Chapter authors:
Mitsuko Masutani, Akemi Gunji, Masahiro Tsutsumi, Kumiko Ogawa, Nobuo Kamada, Tomoyuki Shirai, Kou-ichi Jishage, Hitoshi Nakagama and Takashi Sugimura


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Elucidation of the relationship between poly-ADP-ribosylation and carcinogenesis has markedly progressed by the recent development of knockout or transgenic mice models of poly(ADP-ribose) polymerase (Parp)-1, Parp-2, and poly(ADP-ribose) glycohydrolase (Parg). Parp-1 is involved in base excision repair (BER), single- and double-strand break repair, and chromosomal stability. These multiple functions explain why Parp-1 deficiency enhances carcinogenesis induced by alkylating agents and that in aged animals. Parp-1 is also involved in transcriptional regulation through protein-protein interaction as a coactivator and/or poly-ADP-ribosylation reaction and is possibly involved in epigenetic alteration during carcinogenesis and modulation of tumor phenotypes. Parp-1-dependent cell-death accompanying NAD depletion may be another important issue in carcinogenesis because this process could lead to the selection of Parp-1 deficient cells due to their survival advantage during cancer growth. The relationship of Parp-2, Parp-3, tankyrase and Parg with carcinogenesis is also discussed.

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