TABLE 3.
Classes of DNA damage PARG depletion or inhibition alters cellular toxicity to.
| Class of DNA damage | Method of targeting PARG | Experimental system | Agent | References |
| Alkylating agents | Homozygous deletion of PARG exons 2 and 3 (selective deletion of PARG110) | In vivo | MNU (N-Methyl-N-nitrosourea) Streptozotocin | Cortes et al., 2004 |
| PARG −/− mouse ES cells | In vitro | MNNG (methyl-nitronitrosoguanidine) | Koh et al., 2004 | |
| PARGi (GPI 16552) in metastatic melanoma cancer cells | In vitro and In vivo | Temozolomide | Tentori et al., 2005 | |
| PARGi (Gallotannin) in CHO cells | In vitro | MNNG | Keil et al., 2004 | |
| PARG −/− mouse ES cells | In vitro | Dimethyl Sulfate | Fujihara et al., 2009 | |
| PARG null mouse TS cells | In vitro | MNNG | Zhou et al., 2010 | |
| Cyclo-phosphamide | ||||
| Hypomorphic mutation of PARG leading to PARG110 −/− mouse embryonic fibroblasts | In vitro | MMS (methyl methanesulfonate) | Min et al., 2010 | |
| PARG −/− ES Cells and siRNA in human MIAPaCa2 (pancreas) and RKO (Colon) cancer cell lines | In vitro | MMS | Shirai et al., 2013b | |
| PARGi (PDD00017273) in MCF7 breast cancer cells | In vitro | MMS | James et al., 2016 | |
| PARGi – COH34 in various cancer cell lines | In vitro | Temozolomide | Chen and Yu, 2019 | |
| Cross linking agents | PARG −/− mouse ES cells | In vitro | Cisplatin | Fujihara et al., 2009 |
| PARG null mouse TS cells | In vitro | Cisplatin | Zhou et al., 2010 | |
| PARG −/− ES Cells and siRNA in human MIAPaCa2 (pancreas) and RKO (Colon) cancer cell lines | In vitro | Cisplatin | Shirai et al., 2013b | |
| PARGi (COH34) in various cancer cell lines | In vitro | Cisplatin | Chen and Yu, 2019 | |
| PARGi (PDD00017273) and shRNA in PDAC cell lines | In vitro and in vivo | Oxaliplatin | Jain et al., 2019 | |
| DNA metabolism | PARG −/− mouse ES cells | In vitro | Gemcitabine | Fujihara et al., 2009 |
| PARGi (PDD00017273) in ovarian cancer cell lines | In vitro | Gemcitabine | Pillay et al., 2019 | |
| HU | ||||
| PARGi – (PDD00017273) and shRNA in PDAC cell lines. | In vitro | 5-Fluorouracil | Jain et al., 2019 | |
| Intercalators | PARG null mouse TS cells | In vitro | Epirubicin | Zhou et al., 2010 |
| PARGi (COH34) in various cancer cell lines | In vitro | Doxorubicin | Chen and Yu, 2019 | |
| Incorporated nucleotide analogs | PARG −/− mouse ES cells | In vitro | Gemcitabine | Fujihara et al., 2009 |
| PARGi (PDD00017273) in ovarian cancer cell lines | In vitro | Gemcitabine | Pillay et al., 2019 | |
| Oxidative damage | siRNA in MEFs | In vitro | Hydrogen peroxide | Blenn et al., 2006 |
| siRNA in A549 cancer cell line | In vitro | Hydrogen peroxide | Fisher et al., 2007 | |
| Hypomorphic mutation of PARG leading to PARG110 −/− mouse embryonic fibroblasts | In vitro | Hydrogen peroxide | Min et al., 2010 | |
| Radiation | Homozygous deletion of PARG exons 2 and 3 (deletion of PARG110) | In vivo | γ-Irradiation | Cortes et al., 2004 |
| PARG−/− mouse ES cells | In vitro | γ-Irradiation | Fujihara et al., 2009 | |
| siRNA in HeLa cells | In vitro | X-irradiation | Ame et al., 2009 | |
| Hypomorphic mutation of PARG leading to PARG110 −/− mouse embryonic fibroblasts | In vitro | γ-Irradiation | Min et al., 2010 | |
| PARG−/− mouse ES Cells | In vitro | γ-Irradiation | Shirai et al., 2013a | |
| Carbon ion irradiation | ||||
| Fe-Ion Irradiaiton | ||||
| siRNA, PARGi (PDD00017273) in MCF-7 breast cancer cell line | In vitro | γ-Irradiation | Gravells et al., 2018 | |
| PARGi (JA2131) in prostate cancer PC3 cell line | In vitro | Irradiation | Houl et al., 2019 | |
| Topoisomerases inhibitors | PARG −/− mouse ES cells | In vitro | Camptothecin | Fujihara et al., 2009 |
| shRNA HeLa cell line | In vitro | Camptothecin | Ray Chaudhuri et al., 2015 | |
| PARGi – COH34 in various cancer cell lines | In vitro | Camptothecin | Chen and Yu, 2019 |
Black indicates sensitization by depletion or inhibition, red indicates no difference in response.