REVIEW

The role of PARP1 in the DNA damage response and its application in tumor therapy

  • Zhifeng Wang 1 ,
  • Fengli Wang 2 ,
  • Tieshan Tang , 2 ,
  • Caixia Guo , 1
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  • 1. Laboratory of Disease Genomics and Individual Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China
  • 2. State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

Received date: 26 Sep 2011

Accepted date: 14 Mar 2012

Published date: 05 Jun 2012

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.

Cite this article

Zhifeng Wang , Fengli Wang , Tieshan Tang , Caixia Guo . The role of PARP1 in the DNA damage response and its application in tumor therapy[J]. Frontiers of Medicine, 2012 , 6(2) : 156 -164 . DOI: 10.1007/s11684-012-0197-3

Acknowledgements

We apologize to those investigators whose work we could not cite due to the reference limit, and gratefully acknowledge their contributions to the field. We thank Dr. Paula Fischhaber from California State University Northridge for proof-reading the manuscript. This work was supported by National Natural Science Foundation of China (Grant Nos. 30970588 and 31170730[C.G], Grant No. 30970931[T.S.T]), “One-Hundred-Talent Program”(C.G)and “Knowledge Innovation Program KSCX2-YW-R-148” (T.S.T) from Chinese Academy of Sciences, and National Basic Research Program of China (Nos. 2011CB944302,2011CB965003, 2012CB944702).
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