Skip to main content

Advertisement

SpringerLink
Log in

PARP1-modulated chromatin remodeling is a new target for cancer treatment

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Cancer progression requires certain tumorigenic mutations in genes encoding for different cellular and nuclear proteins. Altered expressions of these mutated genes are mediated by post-translational modifications and chromatin remodeling. Chromatin remodeling is mainly regulated by the chromatin remodeling enzyme complexes and histone modifications. Upon DNA damage, Poly-(ADP-ribose) Polymerase1 (PARP1) plays a very important role in the induction of chromatin modifications and activation of DNA repair pathways to repair the DNA lesion. It has been targeted to develop different anti-cancer therapeutic interventions and PARP inhibitors have been approved by the U.S. Food and Drug Administration (FDA) for clinical use. But it has been found that the cancer cells often develop resistance to these PARP inhibitors and chromatin remodeling helps in enhancing this process. Hence, it may be beneficial to target PARP1-mediated chromatin remodeling, which may allow to reverse the drug resistance. In the current review, we have discussed the role of chromatin remodeling in DNA repair, how PARP1 regulates modifications of chromatin dynamics, and the role of chromatin modifications in cancer. It has also been discussed how the PARP1-mediated chromatin remodeling can be targeted by PARP inhibitors alone or in combination with other chemotherapeutic agents to establish novel anti-cancer therapeutics. We have also considered the use of PARG inhibitors that may enhance the action of PARP inhibitors to target different types of cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Availability of data and materials

All the information mentioned in this review article are available on the internet.

Code availability

Not applicable.

References

  1. Pandey SM. Chromatin remodeling complexes: the regulators of genome function. Glob J Zool. 2016;1(1):7–13. https://doi.org/10.17352/gjz.000003.

    Article  Google Scholar 

  2. Narlikar GJ, Sundaramoorthy R, Owen-Hughes T. Mechanisms and functions of ATP-dependent chromatin-remodeling enzymes. Cell. 2013;154:490–503. https://doi.org/10.1016/j.cell.2013.07.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liu C, Vyas A, Kassab MA, Singh AK, Yu X. The role of poly ADP-ribosylation in the first wave of DNA damage response. Nucleic Acids Res. 2017;45(14):8129–41. https://doi.org/10.1093/nar/gkx565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hottiger MO, Hassa PO, Lüscher B, Schüler H, Koch-Nolte F. Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem Sci. 2010;35(4):208–19. https://doi.org/10.1016/j.tibs.2009.12.003.

    Article  CAS  PubMed  Google Scholar 

  5. D’Amours D, Desnoyers S, D’Silva I, Poirier GG. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999;342(2):249–68. https://doi.org/10.1042/bj3420249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hassa PO, Haenni SS, Elser M, Hottiger MO. Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiol Mol Biol Rev. 2006;70(3):789–829. https://doi.org/10.1128/MMBR.00040-05.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Luo X, Kraus WL. On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev. 2012;26(5):417–32. https://doi.org/10.1101/gad.183509.111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Barkauskaite E, Jankevicius G, Ahel I. Structures and mechanisms of enzymes employed in the synthesis and degradation of PARP-dependent protein ADP-ribosylation. Mol Cell. 2015;58(6):935–46. https://doi.org/10.1016/j.molcel.2015.05.007.

    Article  CAS  PubMed  Google Scholar 

  9. Ciccarone F, Zampieri M, Caiafa P. PARP1 orchestrates epigenetic events setting up chromatin domains. Semin Cell Dev Biol. 2017;63:123–34. https://doi.org/10.1016/j.semcdb.2016.11.010.

    Article  CAS  PubMed  Google Scholar 

  10. Quénet D, El Ramy R, Schreiber V, Dantzer F. The role of poly(ADP-ribosyl)ation in epigenetic events. Int J Biochem Cell Biol. 2009;41(1):60–5. https://doi.org/10.1016/j.biocel.2008.07.023.

    Article  CAS  PubMed  Google Scholar 

  11. Morgan MA, Shilatifard A. Chromatin signatures of cancer. Genes Dev. 2015;29:238–49. https://doi.org/10.1101/gad.255182.114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Manelyte L, Langst G. Chromatin remodelers and their way of action. In: Radzioch D, editor. Chromatin remodelling. Rijeka: IntechOpen; 2013.

    Google Scholar 

  13. Costello KR, Schones DE. Chromatin modifications in metabolic disease: potential mediators of long-term disease risk. Wiley Interdiscip Rev Syst Biol Med. 2018;10(4): e1416. https://doi.org/10.1002/wsbm.1416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Audia JE, Campbell RM. Histone Modifications and Cancer. Cold Spring Harb Perspect Biol. 2016;8(4): a019521. https://doi.org/10.1101/cshperspect.a019521.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Clapier CR, Iwasa J, Cairns BR, Peterson CL. Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat Rev Mol Cell Biol. 2017;18(7):407–22. https://doi.org/10.1038/nrm.2017.26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mayes K, Qiu Z, Alhazmi A, Landry JW. ATP-dependent chromatin remodeling complexes as novel targets for cancer therapy. Adv Cancer Res. 2014;121:183–233. https://doi.org/10.1016/B978-0-12-800249-0.00005-6.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen. 2017;58(5):235–63. https://doi.org/10.1002/em.22087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dinant C, Houtsmuller AB, Vermeulen W. Chromatin structure and DNA damage repair. Epigenet Chromatin. 2008;1(1):9. https://doi.org/10.1186/1756-8935-1-9.

    Article  CAS  Google Scholar 

  19. Polo SE, Almouzni G. Chromatin dynamics after DNA damage: the legacy of the access-repair-restore model. DNA Repair (Amst). 2015;36:114–21. https://doi.org/10.1016/j.dnarep.2015.09.014.

    Article  CAS  Google Scholar 

  20. Nair N, Shoaib M, Sørensen CS. Chromatin dynamics in genome stability: roles in suppressing endogenous DNA damage and facilitating DNA repair. Int J Mol Sci. 2017;18(7):1486. https://doi.org/10.3390/ijms18071486.

    Article  CAS  PubMed Central  Google Scholar 

  21. Price BD, D’Andrea AD. Chromatin remodeling at DNA double-strand breaks. Cell. 2013;152(6):1344–54. https://doi.org/10.1016/j.cell.2013.02.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Luijsterburg MS, de Krijger I, Wiegant WW, et al. PARP1 links CHD2-mediated chromatin expansion and H3.3 deposition to DNA repair by non-homologous end-joining. Mol Cell. 2016;61(4):547–62. https://doi.org/10.1016/j.molcel.2016.01.019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Poirier GG, de Murcia G, Jongstra-Bilen J, Niedergang C, Mandel P. Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure. Proc Natl Acad Sci U S A. 1982;79(11):3423–7. https://doi.org/10.1073/pnas.79.11.3423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Messner S, Altmeyer M, Zhao H, et al. PARP1 ADP-ribosylates lysine residues of the core histone tails. Nucleic Acids Res. 2010;38(19):6350–62. https://doi.org/10.1093/nar/gkq463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Naegeli H, Althaus FR. Regulation of poly(ADP-ribose) polymerase. Histone-specific adaptations of reaction products. J Biol Chem. 1991;266(16):10596–601. https://doi.org/10.1016/S0021-9258(18)99265-3.

    Article  CAS  PubMed  Google Scholar 

  26. Pinnola A, Naumova N, Shah M, Tulin AV. Nucleosomal core histones mediate dynamic regulation of poly (ADP-ribose) polymerase 1 protein binding to chromatin and induction of its enzymatic activity. J Biol Chem. 2007;282(44):32511–9. https://doi.org/10.1074/jbc.M705989200.

    Article  CAS  PubMed  Google Scholar 

  27. Kim MY, Mauro S, Gévry N, Lis JT, Kraus WL. NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell. 2004;119(6):803–14. https://doi.org/10.1016/j.cell.2004.11.002.

    Article  CAS  PubMed  Google Scholar 

  28. Clark NJ, Kramer M, Muthurajan UM, Luger K. Alternative modes of binding of poly (ADP-ribose) polymerase 1 to free DNA and nucleosomes. J Biol Chem. 2012;287(39):32430–9. https://doi.org/10.1074/jbc.M112.397067.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Muthurajan UM, Hepler MR, Hieb AR, Clark NJ, Kramer M, Yao T, Luger K. Automodification switches PARP-1 function from chromatin architectural protein to histone chaperone. Proc Natl Acad Sci USA. 2014;111(35):12752–7. https://doi.org/10.1073/pnas.1405005111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rouleau M. Poly(ADP-ribosyl)ated chromatin domains: access granted. J Cell Sci. 2004;117:815–25. https://doi.org/10.1242/jcs.01080.

    Article  CAS  PubMed  Google Scholar 

  31. Malik N, Smulson M. A relationship between nuclear poly (adenosine diphosphate ribosylation) and acetylation posttranslational modifications. 1. Nucleosome studies. Biochemistry. 1984;23(16):3721–5. https://doi.org/10.1021/bi00311a023.

    Article  CAS  PubMed  Google Scholar 

  32. Cohen-Armon M, Visochek L, Rozensal D, et al. DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation. Mol Cell. 2007;25(2):297–308. https://doi.org/10.1016/j.molcel.2006.12.012.

    Article  CAS  PubMed  Google Scholar 

  33. Verdone L, La Fortezza M, Ciccarone F, Caiafa P, Zampieri M, Caserta M. Poly (ADP-ribosyl) ation affects histone acetylation and transcription. PLoS ONE. 2015;10(12): e0144287. https://doi.org/10.1371/journal.pone.0144287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hassa PO, Haenni SS, Buerki C, et al. Acetylation of poly (ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-κB-dependent transcription. J Biol Chem. 2005;280(49):40450–64. https://doi.org/10.1074/jbc.M507553200.

    Article  CAS  PubMed  Google Scholar 

  35. Cantó C, Sauve AA, Bai P. Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes. Mol Aspects Med. 2013;34(6):1168–201. https://doi.org/10.1016/j.mam.2013.01.004.

    Article  CAS  PubMed  Google Scholar 

  36. Ruthenburg AJ, Allis CD, Wysocka J. Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. Mol Cell. 2007;25(1):15–30. https://doi.org/10.1016/j.molcel.2006.12.014.

    Article  CAS  PubMed  Google Scholar 

  37. Li X, Liu L, Yang S, et al. Histone demethylase KDM5B is a key regulator of genome stability. Proc Natl Acad Sci U S A. 2014;111(19):7096–101. https://doi.org/10.1073/pnas.1324036111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gong F, Clouaire T, Aguirrebengoa M, Legube G, Miller KM. Histone demethylase KDM5A regulates the ZMYND8-NuRD chromatin remodeler to promote DNA repair. J Cell Biol. 2017;216(7):1959–74. https://doi.org/10.1083/jcb.201611135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Krishnan S, Horowitz S, Trievel RC. Structure and function of histone H3 lysine 9 methyltransferases and demethylases. ChemBioChem. 2011;12(2):254–63. https://doi.org/10.1002/cbic.201000545.

    Article  CAS  PubMed  Google Scholar 

  40. Le May N, Iltis I, Amé JC, et al. Poly (ADP-ribose) glycohydrolase regulates retinoic acid receptor-mediated gene expression. Mol Cell. 2012;48(5):785–98. https://doi.org/10.1016/j.molcel.2012.09.021.

    Article  CAS  PubMed  Google Scholar 

  41. Khoury-Haddad H, Guttmann-Raviv N, Ipenberg I, Huggins D, Jeyasekharan AD, Ayoub N. PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair. Proc Natl Acad Sci U S A. 2014;111(7):E728–37. https://doi.org/10.1073/pnas.1317585111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Martin KA, Cesaroni M, Denny MF, Lupey LN, Tempera I. Global transcriptome analysis reveals that poly(ADP-Ribose) polymerase 1 regulates gene expression through EZH2. Mol Cell Biol. 2015;35(23):3934–44. https://doi.org/10.1128/MCB.00635-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Campbell S, Ismail IH, Young LC, Poirier GG, Hendzel MJ. Polycomb repressive complex 2 contributes to DNA double-strand break repair. Cell Cycle. 2013;12(16):2675–83. https://doi.org/10.4161/cc.25795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Schübeler D. Function and information content of DNA methylation. Nature. 2015;517(7534):321–6. https://doi.org/10.1038/nature14192.

    Article  CAS  PubMed  Google Scholar 

  45. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21. https://doi.org/10.1101/gad.947102.

    Article  CAS  PubMed  Google Scholar 

  46. Clark AT. DNA methylation remodeling in vitro and in vivo. Curr Opin Genet Dev. 2015;34:82–7. https://doi.org/10.1016/j.gde.2015.09.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003;349(21):2042–54. https://doi.org/10.1056/NEJMra023075.

    Article  CAS  PubMed  Google Scholar 

  48. Reale A, Matteis GD, Galleazzi G, Zampieri M, Caiafa P. Modulation of DNMT1 activity by ADP-ribose polymers. Oncogene. 2005;24(1):13–9. https://doi.org/10.1038/sj.onc.1208005.

    Article  CAS  PubMed  Google Scholar 

  49. Caiafa P, Guastafierro T, Zampieri M. Epigenetics: poly(ADP-ribosyl)ation of PARP-1 regulates genomic methylation patterns. FASEB J. 2009;23(3):672–8. https://doi.org/10.1096/fj.08-123265.

    Article  CAS  PubMed  Google Scholar 

  50. Zampieri M, Guastafierro T, Calabrese R, et al. ADP-ribose polymers localized on Ctcf-Parp1-Dnmt1 complex prevent methylation of Ctcf target sites. Biochem J. 2012;441(2):645–52. https://doi.org/10.1042/BJ20111417.

    Article  CAS  PubMed  Google Scholar 

  51. Guastafierro T, Catizone A, Calabrese R, et al. ADP-ribose polymer depletion leads to nuclear Ctcf re-localization and chromatin rearrangement(1). Biochem J. 2013;449(3):623–30. https://doi.org/10.1042/BJ20121429.

    Article  CAS  PubMed  Google Scholar 

  52. Nalabothula N, Al-jumaily T, Eteleeb AM, et al. Genome-wide profiling of PARP1 reveals an interplay with gene regulatory regions and DNA methylation. PLoS ONE. 2015;10(8): e0135410. https://doi.org/10.1371/journal.pone.0135410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Andronikou C, Rottenberg S. Studying PAR-dependent chromatin remodeling to tackle PARPi resistance. Trends Mol Med. 2021;27(7):630–42. https://doi.org/10.1016/j.molmed.2021.04.010.

    Article  CAS  PubMed  Google Scholar 

  54. Singh HR, Nardozza AP, Möller IR, et al. A poly-ADP-ribose trigger releases the auto-inhibition of a chromatin remodeling oncogene. Mol Cell. 2017;68(5):860-71.e7. https://doi.org/10.1016/j.molcel.2017.11.019.

    Article  CAS  PubMed  Google Scholar 

  55. Blessing C, Mandemaker IK, Gonzalez-Leal C, Preisser J, Schomburg A, Ladurner AG. The oncogenic helicase ALC1 regulates PARP inhibitor potency by trapping PARP2 at DNA breaks. Mol Cell. 2020;80(5):862-75.e6. https://doi.org/10.1016/j.molcel.2020.10.009.

    Article  CAS  PubMed  Google Scholar 

  56. Mehrotra PV, Ahel D, Ryan DP, et al. DNA repair factor APLF is a histone chaperone. Mol Cell. 2011;41(1):46–55. https://doi.org/10.1016/j.molcel.2010.12.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Xu C, Xu Y, Gursoy-Yuzugullu O, Price BD. The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1. FEBS Lett. 2012;586(21):3920–5. https://doi.org/10.1016/j.febslet.2012.09.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ruiz PD, Hamilton GA, Park JW, Gamble MJ. MacroH2A1 regulation of poly(ADP-Ribose) synthesis and stability prevents necrosis and promotes DNA repair. Mol Cell Biol. 2019;40(1):e00230-e319. https://doi.org/10.1128/MCB.00230-19.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Smeenk G, Wiegant WW, Marteijn JA, et al. Poly(ADP-ribosyl)ation links the chromatin remodeler SMARCA5/SNF2H to RNF168-dependent DNA damage signaling. J Cell Sci. 2013;126(4):889–903. https://doi.org/10.1242/jcs.109413.

    Article  CAS  PubMed  Google Scholar 

  60. Chou DM, Adamson B, Dephoure NE, et al. A chromatin localization screen reveals poly (ADP ribose)-regulated recruitment of the repressive polycomb and NuRD complexes to sites of DNA damage. Proc Natl Acad Sci U S A. 2010;107(43):18475–80. https://doi.org/10.1073/pnas.1012946107.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Silva AP, Ryan DP, Galanty Y, et al. The N-terminal region of chromodomain helicase DNA-binding protein 4 (CHD4) is essential for activity and contains a high mobility group (HMG) box-like-domain that can bind poly(ADP-ribose). J Biol Chem. 2016;291(2):924–38. https://doi.org/10.1074/jbc.M115.683227.

    Article  CAS  PubMed  Google Scholar 

  62. Pan MR, Hsieh HJ, Dai H, et al. Chromodomain helicase DNA-binding protein 4 (CHD4) regulates homologous recombination DNA repair, and its deficiency sensitizes cells to poly(ADP-ribose) polymerase (PARP) inhibitor treatment. J Biol Chem. 2012;287(9):6764–72. https://doi.org/10.1074/jbc.M111.287037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lebeaupin T, Smith R, Huet S, Timinszky G. Poly(ADP-Ribose)-dependent chromatin remodeling in DNA repair. Methods Mol Biol. 2017;1608:165–83. https://doi.org/10.1007/978-1-4939-6993-7_12.

    Article  CAS  PubMed  Google Scholar 

  64. Min A, Im SA. PARP Inhibitors as therapeutics: Beyond modulation of PARylation. Cancers (Basel). 2020;12(2):394. https://doi.org/10.3390/cancers12020394.

    Article  CAS  Google Scholar 

  65. Murai J, Huang SY, Das BB, et al. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res. 2012;72(21):5588–99. https://doi.org/10.1158/0008-5472.CAN-12-2753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Chabanon RM, Morel D, Eychenne T, et al. PBRM1 deficiency confers synthetic lethality to DNA repair inhibitors in cancer. Cancer Res. 2021;81(11):2888–902. https://doi.org/10.1158/0008-5472.CAN-21-0628.

    Article  CAS  PubMed  Google Scholar 

  67. Verma P, Zhou Y, Cao Z, et al. ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells. Nat Cell Biol. 2021;23(2):160–71. https://doi.org/10.1038/s41556-020-00624-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hewitt G, Borel V, Segura-Bayona S, et al. Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD. Mol Cell. 2021;81(4):767-83.e11. https://doi.org/10.1016/j.molcel.2020.12.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tsuda M, Cho K, Ooka M, et al. ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair. PLoS ONE. 2017;12(11): e0188320. https://doi.org/10.1371/journal.pone.0188320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zhou Q, Huang J, Zhang C, et al. The bromodomain containing protein BRD-9 orchestrates RAD51-RAD54 complex formation and regulates homologous recombination-mediated repair. Nat Commun. 2020;11(1):2639. https://doi.org/10.1038/s41467-020-16443-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Park Y, Chui MH, Suryo Rahmanto Y, et al. Loss of ARID1A in tumor cells renders selective vulnerability to combined ionizing radiation and PARP inhibitor therapy. Clin Cancer Res. 2019;25(18):5584–94. https://doi.org/10.1158/1078-0432.CCR-18-4222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wang F, Zhu S, Fisher LA, et al. Phosphatase 1 nuclear targeting subunit mediates recruitment and function of poly (ADP-Ribose) polymerase 1 in DNA repair. Cancer Res. 2019;79(10):2526–35. https://doi.org/10.1158/0008-5472.CAN-18-1673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Molla S, Chatterjee S, Sethy C, Sinha S, Kundu CN. Olaparib enhances curcumin-mediated apoptosis in oral cancer cells by inducing PARP trapping through modulation of BER and chromatin assembly. DNA Repair (Amst). 2021;105: 103157. https://doi.org/10.1016/j.dnarep.2021.103157.

    Article  CAS  Google Scholar 

  74. Kim Y, Kim A, Sharip A, et al. Reverse the resistance to PARP inhibitors. Int J Biol Sci. 2017;13:198–208. https://doi.org/10.7150/ijbs.17240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Liu Y, Martin-Trevino R, Shang L, et al. Histone deacetylase inhibitors sensitize cancer stem cells to PARP inhibitors in triple-negative breast cancer. [abstract] In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research. Cancer Res. 2017;75(15):4226. https://doi.org/10.1158/1538-7445.AM2015-4226.

    Article  Google Scholar 

  76. Yin L, Liu Y, Peng Y, et al. PARP inhibitor veliparib and HDAC inhibitor SAHA synergistically co-target the UHRF1/BRCA1 DNA damage repair complex in prostate cancer cells. J Exp Clin Cancer Res. 2018;37(1):153. https://doi.org/10.1186/s13046-018-0810-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Valdez BC, Li Y, Murray D, et al. Combination of a hypomethylating agent and inhibitors of PARP and HDAC traps PARP1 and DNMT1 to chromatin, acetylates DNA repair proteins, down-regulates NuRD and induces apoptosis in human leukemia and lymphoma cells. Oncotarget. 2017;9(3):3908–21. https://doi.org/10.18632/oncotarget.23386.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Yamamoto M, Jin C, Hata T, et al. MUC1-C integrates chromatin remodeling and PARP1 activity in the DNA damage response of triple-negative breast cancer cells. Cancer Res. 2019;79(8):2031–41. https://doi.org/10.1158/0008-5472.CAN-18-3259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kaur J, Daoud A, Eblen ST. Targeting chromatin remodeling for cancer therapy. Curr Mol Pharmacol. 2019;12(3):215–29. https://doi.org/10.2174/1874467212666190215112915.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Slade D. PARP and PARG inhibitors in cancer treatment. Genes Dev. 2020;34(5–6):360–94. https://doi.org/10.1101/gad.334516.119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Falsig J, Christiansen SH, Feuerhahn S, et al. Poly(ADP-ribose) glycohydrolase as a target for neuroprotective intervention: assessment of currently available pharmacological tools. Eur J Pharmacol. 2004;497(1):7–16. https://doi.org/10.1016/j.ejphar.2004.06.042.

    Article  CAS  PubMed  Google Scholar 

  82. Erdèlyi K, Kiss A, Bakondi E, et al. Gallotannin inhibits the expression of chemokines and inflammatory cytokines in A549 cells. Mol Pharmacol. 2005;68(3):895–904. https://doi.org/10.1124/mol.105.012518.

    Article  CAS  PubMed  Google Scholar 

  83. Slama JT, Aboul-Ela N, Goli DM, et al. Specific inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol. J Med Chem. 1995;38(2):389–93. https://doi.org/10.1021/jm00002a021.

    Article  CAS  PubMed  Google Scholar 

  84. Finch KE, Knezevic CE, Nottbohm AC, et al. Selective small molecule inhibition of poly(ADP-ribose) glycohydrolase (PARG). ACS Chem Biol. 2012;7(3):563–70. https://doi.org/10.1021/cb200506t.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. James DI, Smith KM, Jordan AM, et al. First-in-class chemical probes against poly(ADP-ribose) glycohydrolase (PARG) Inhibit DNA repair with differential pharmacology to olaparib. ACS Chem Biol. 2016;11(11):3179–90. https://doi.org/10.1021/acschembio.6b00609.

    Article  CAS  PubMed  Google Scholar 

  86. Pillay N, Tighe A, Nelson L, et al. DNA replication vulnerabilities render ovarian cancer cells sensitive to poly(ADP-Ribose) glycohydrolase inhibitors. Cancer Cell. 2019;35(3):519-533.e8. https://doi.org/10.1016/j.ccell.2019.02.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Chen SH, Yu X. Targeting dePARylation selectively suppresses DNA repair-defective and PARP inhibitor-resistant malignancies. Sci Adv. 2019;5(4):eaav4340. https://doi.org/10.1126/sciadv.aav4340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Houl JH, Ye Z, Brosey CA, et al. Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death. Nat Commun. 2019;10(1):5654. https://doi.org/10.1038/s41467-019-13508-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Jain A, Agostini LC, McCarthy GA, et al. Poly (ADP) ribose glycohydrolase can be effectively targeted in pancreatic cancer. Cancer Res. 2019;79(17):4491–502. https://doi.org/10.1158/0008-5472.CAN-18-3645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the Department of Biotechnology (DBT), Government of India, for providing research funding to CNK. They would also like to thank the Indian Council of Medical research (ICMR), Government of India, and Government of Ethiopia for providing research fellowships to SS and SM, respectively.

Funding

This work was partly funded by the Department of Biotechnology (DBT), Government of India (102/IFD/SAN/703/2018–2018).

Author information

Author notes

  1. Saptarshi Sinha and Sefinew Molla have equally contributed to this work.

Authors and Affiliations

  1. Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Campus-11, Patia, Bhubaneswar, Odisha, 751024, India

    Saptarshi Sinha, Sefinew Molla & Chanakya Nath Kundu

Authors
  1. Saptarshi Sinha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sefinew Molla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chanakya Nath Kundu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SS and SM contributed equally to the conception, design, and drafting of the manuscript. CNK critically reviewed the manuscript and approved the final submitted version.

Corresponding author

Correspondence to Chanakya Nath Kundu.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethical approval

Ethical approval was not required for this review article.

Consent to participate

Not applicable.

Consent to publish

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sinha, S., Molla, S. & Kundu, C.N. PARP1-modulated chromatin remodeling is a new target for cancer treatment. Med Oncol 38, 118 (2021). https://doi.org/10.1007/s12032-021-01570-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-021-01570-2

Keywords

Search

Navigation