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

doi:10.1007/s11684-012-0197-3

Front Med

2012, Vol. 6

Issue (2) : 156-164 https://doi.org/10.1007/s11684-012-0197-3

REVIEW

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

Zhifeng Wang¹, Fengli Wang², Tieshan Tang²(

), Caixia Guo¹(

)

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

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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.

Keywords PARP1 synthetic lethality PARP inhibitor DNA repair cancer NHEJ

Corresponding Author(s): Tang Tieshan,Email:tangtsh@ioz.ac.cn; Guo Caixia,Email:guocx@big.ac.cn

Issue Date: 05 June 2012

Cite this article:

Zhifeng Wang,Fengli Wang,Tieshan Tang, et al. The role of PARP1 in the DNA damage response and its application in tumor therapy[J]. Front Med, 2012, 6(2): 156-164.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-012-0197-3
https://academic.hep.com.cn/fmd/EN/Y2012/V6/I2/156

Fig.1 Schematic representation of human PARP1.
Zn: zinc finger motif; NLS: nuclear localization signal; BRCT: the breast cancer suppressor protein–1 (BRCA1) C-terminal domain; WGR: a domain with a most conserved motif (W/G/R).

Fig.2 The models of SSBR and HR repair initiated by PARP1. The left panel is SSBR, and the right panel is HR.

Fig.3 Schematic model of NHEJ. Left panel: D-NHEJ; right panel: B-NHEJ.

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