Abstract
Poly-ADP-ribosylation of proteins, mediated by the two ADP-ribosyltransferases PARP1 and PARP2 in response to DNA damage, has emerged as a critical mediator of the DNA damage response (DDR). Accordingly, considering the critical role of DDR in cancer, PARP inhibitors (PARPi) have become an important class of therapeutics. PARPi have largely been considered for their intrinsic actions to tumor cells per se. However, these compounds also affect the immune response to tumors. It is now an emerging evidence supporting immunomodulatory roles of PARP1 and PARP2 which can facilitate or impede tumor progression. In this chapter, we describe some protocols to study the immunomodulatory functions of PARP1 and PARP2 in mouse tumor models.
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References
Lüscher B, Ahel I, Altmeyer M, Ashworth A, Bai P, Chang P et al (2021) ADP-ribosyltransferases, an update on function and nomenclature. FEBS J. https://doi.org/10.1111/febs.16142
Yelamos J, Farres J, Llacuna L, Ampurdanes C, Martin-Caballero J (2011) PARP1 and PARP2: new players in tumour development. Am J Cancer Res 1:328–346
Ménissier de Murcia J, Ricoul M, Tartier L, Niedergang C, Huber A, Dantzer F et al (2003) Functional interaction between PARP1 and PARP2 in chromosome stability and embryonic development in mouse. EMBO J 22:2255–2263. https://doi.org/10.1093/emboj/cdg206
de Murcia JM, Niedergang C, Trucco C, Ricoul M, Dutrillaux B, Mark M et al (1997) Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proc Natl Acad Sci U S A 94:7303–7307. https://doi.org/10.1073/pnas.94.14.7303
Slade D (2020) PARP and PARG inhibitors in cancer treatment. Genes Dev 34:360–394. https://doi.org/10.1101/gad.334516.119
Farrés J, Llacuna L, Martin-Caballero J, Martínez C, Lozano JJ, Ampurdanés C et al (2015) PARP2 sustains erythropoiesis in mice by limiting replicative stress in erythroid progenitors. Cell Death Differ 22:1144–1157. https://doi.org/10.1038/cdd.2014.202
Galindo-Campos MA, Lutfi N, Bonnin S, Martínez C, Velasco-Hernández T, García-Hernández V et al (2022) Distinct roles for PARP1 and PARP2 in c-Myc-driven B-cell lymphoma in mice. Blood 139:228–239. https://doi.org/10.1182/blood.2021012805
Yélamos J, Monreal Y, Saenz L, Aguado E, Schreiber V, Mota R et al (2006) PARP2 deficiency affects the survival of CD4+CD8+ double-positive thymocytes. EMBO J 25:4350–4360. https://doi.org/10.1038/sj.emboj.7601301
Dantzer F, Mark M, Quenet D, Scherthan H, Huber A, Liebe B et al (2006) Poly(ADP-ribose) polymerase-2 contributes to the fidelity of male meiosis I and spermiogenesis. Proc Natl Acad Sci 103:14854–14859. https://doi.org/10.1073/pnas.0604252103
Gibson BA, Zhang Y, Jiang H, Hussey KM, Shrimp JH, Lin H et al (2016) Chemical genetic discovery of PARP targets reveals a role for PARP1 in transcription elongation. Science 353:45–50. https://doi.org/10.1126/science.aaf7865
Ali SO, Khan FA, Galindo-Campos MA, Yélamos J (2016) Understanding specific functions of PARP2: new lessons for cancer therapy. Am J Cancer Res 6:1842–1863
Lutfi N, Galindo-Campos MA, Yélamos J (2021) Impact of DNA damage response-targeted therapies on the immune response to tumours. Cancers (Basel) 13:6008. https://doi.org/10.3390/cancers13236008
Boehler C, Gauthier L, Yelamos J, Noll A, Schreiber V, Dantzer F (2011) Phenotypic characterization of PARP1 and PARP2 deficient mice and cells. Methods Mol Biol 780:313–336. https://doi.org/10.1007/978-1-61779-270-0_19
Acknowledgments
The Yélamos lab is funded by the Spanish Ministerio de Ciencia e Innovación (grant PID2020-112526RB-I00, funded by MCIN/AEI/10.13039/501100011033).
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Lutfi, N., Martínez, C., Yélamos, J. (2023). Studying the Immunomodulatory Functions of PARP1 and PARP2 in Mouse Models of Cancer. In: Tulin, A.V. (eds) Poly(ADP-Ribose) Polymerase. Methods in Molecular Biology, vol 2609. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2891-1_12
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DOI: https://doi.org/10.1007/978-1-0716-2891-1_12
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