Due to endogenous and exogenous factors, such as UV radiation, ionizing radiation and genotoxic chemicals, DNA in every cell of the body is at constant risk of damage [1-3]. To overcome damage to DNA, repair pathways are needed. These pathways are collectively referred to as DNA damage response (DDR) [1, 4].
Click here for more information about the DDR.
PARP is involved in DDR via several mechanisms [5-7]:
- Repair of double-strand breaks through homologous recombination repair (HRR)
- Non-homologous end joining (NHEJ)
- Micro-homology mediated end joining (MMEJ; also known as alt-NHEJ).
- Repair of single strand breaks (SSB) via base excision repair (BER).
Click here to find out more on what happens at the molecular level.
- Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature 2012; 481: 287-294.
- Friedberg EC. A brief history of the DNA repair field. Cell Res 2008; 18: 3-7.
- Ashworth A. A synthetic lethal therapeutic approach: poly(ADP) ribose polymerase inhibitors for the treatment of cancers deficient in DNA double-strand break repair. J Clin Oncol 2008; 26: 3785-3790.
- Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science 2017; 355: 1152-1158.
- Moynahan ME, Jasin M. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol 2010; 11: 196-207.
- Murai J, Huang SY, Das BB et al. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res 2012; 72: 5588-5599.
- Cerrato A, Morra F, Celetti A. Use of poly ADP-ribose polymerase [PARP] inhibitors in cancer cells bearing DDR defects: the rationale for their inclusion in the clinic. J Exp Clin Cancer Res 2016; 35: 179.