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Gundogdu R, Erdogan MK, Ditsiou A, et al. hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors. Cell Signal. 2021;87:110106doi: 10.1016/j.cellsig.2021.110106.
Gundogdu, R., Erdogan, M. K., Ditsiou, A., Spanswick, V., Garcia-Gomez, J. J., Hartley, J. A., Esashi, F., Hergovich, A., & Gomez, V. (2021). hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors. Cellular signalling, 87110106. https://doi.org/10.1016/j.cellsig.2021.110106
Gundogdu, Ramazan, et al. "hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors." Cellular signalling vol. 87 (2021): 110106. doi: https://doi.org/10.1016/j.cellsig.2021.110106
Gundogdu R, Erdogan MK, Ditsiou A, Spanswick V, Garcia-Gomez JJ, Hartley JA, Esashi F, Hergovich A, Gomez V. hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors. Cell Signal. 2021 Nov;87:110106. doi: 10.1016/j.cellsig.2021.110106. Epub 2021 Aug 05. PMID: 34363951; PMCID: PMC8514680.
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Cell Signal. 2021 Nov;87:110106. doi: 10.1016/j.cellsig.2021.110106. Epub 2021 Aug 05.

hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors.

Cellular signalling

Ramazan Gundogdu, M Kadir Erdogan, Angeliki Ditsiou, Victoria Spanswick, Juan Jose Garcia-Gomez, John A Hartley, Fumiko Esashi, Alexander Hergovich, Valenti Gomez

Affiliations

  1. Department of Biology, Bingol University, Bingol 12000, Turkey; UCL Cancer Institute, University College London, London WC1E 6DD, UK. Electronic address: [email protected].
  2. Department of Biology, Bingol University, Bingol 12000, Turkey.
  3. Department of Biochemistry and Biomedicine, University of Sussex, Brighton BN1 9QG, UK; UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  4. UCL Cancer Institute, University College London, London WC1E 6DD, UK.
  5. Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
  6. UCL Cancer Institute, University College London, London WC1E 6DD, UK; Evotec France, Toulouse 31100, France.
  7. UCL Cancer Institute, University College London, London WC1E 6DD, UK. Electronic address: [email protected].

PMID: 34363951 PMCID: PMC8514680 DOI: 10.1016/j.cellsig.2021.110106

Abstract

Monopolar spindle-one binder (MOBs) proteins are evolutionarily conserved and contribute to various cellular signalling pathways. Recently, we reported that hMOB2 functions in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest in untransformed cells. However, the question of how hMOB2 protects cells from endogenous DNA damage accumulation remained enigmatic. Here, we uncover hMOB2 as a regulator of double-strand break (DSB) repair by homologous recombination (HR). hMOB2 supports the phosphorylation and accumulation of the RAD51 recombinase on resected single-strand DNA (ssDNA) overhangs. Physiologically, hMOB2 expression supports cancer cell survival in response to DSB-inducing anti-cancer compounds. Specifically, loss of hMOB2 renders ovarian and other cancer cells more vulnerable to FDA-approved PARP inhibitors. Reduced MOB2 expression correlates with increased overall survival in patients suffering from ovarian carcinoma. Taken together, our findings suggest that hMOB2 expression may serve as a candidate stratification biomarker of patients for HR-deficiency targeted cancer therapies, such as PARP inhibitor treatments.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: DNA damage response signalling; Homologous recombination DNA repair; Mps one binder 2 (MOB2); Personalised PARP inhibitor treatments

References

  1. Nature. 2005 Apr 14;434(7035):913-7 - PubMed
  2. Nat Rev Cancer. 2008 Mar;8(3):193-204 - PubMed
  3. Mol Cell. 2015 Nov 19;60(4):547-60 - PubMed
  4. Methods Mol Biol. 2010;613:267-82 - PubMed
  5. Nucleic Acids Res. 2006 Mar 23;34(6):1685-91 - PubMed
  6. Clin Cancer Res. 2019 Jul 1;25(13):3759-3771 - PubMed
  7. Nucleic Acids Res. 2008 Jun;36(11):3781-90 - PubMed
  8. Cell Res. 2008 Jan;18(1):134-47 - PubMed
  9. Cell Signal. 2015 Feb;27(2):326-39 - PubMed
  10. J Cell Biol. 2016 Feb 1;212(3):281-8 - PubMed
  11. Cells. 2019 Jun 10;8(6): - PubMed
  12. Mol Cell. 2020 Jun 18;78(6):1070-1085 - PubMed
  13. Sci Rep. 2015 Jun 09;5:10449 - PubMed
  14. Methods Mol Biol. 2012;920:379-91 - PubMed
  15. Structure. 2003 Sep;11(9):1163-70 - PubMed
  16. Clin Cancer Res. 2020 Mar 15;26(6):1372-1384 - PubMed
  17. EMBO J. 2008 May 7;27(9):1368-77 - PubMed
  18. Mol Cell Biol. 2010 Sep;30(18):4507-20 - PubMed
  19. Clin Cancer Res. 2016 Dec 1;22(23):5651-5660 - PubMed
  20. Science. 2017 Mar 17;355(6330):1152-1158 - PubMed
  21. Cell. 2011 Mar 4;144(5):646-74 - PubMed
  22. Nature. 2005 Mar 31;434(7033):598-604 - PubMed
  23. Sci Signal. 2010 Jun 15;3(126):ra47 - PubMed
  24. Mol Cell. 2007 Feb 23;25(4):625-34 - PubMed
  25. Front Oncol. 2019 Dec 10;9:1388 - PubMed
  26. Curr Biol. 2015 Oct 5;25(19):2479-92 - PubMed
  27. Front Cell Neurosci. 2018 Mar 12;12:57 - PubMed
  28. Cell Signal. 2015 Aug;27(8):1569-75 - PubMed
  29. Biochem Biophys Res Commun. 2015 Jun 5;461(3):543-8 - PubMed
  30. Nat Genet. 2001 Mar;27(3):247-54 - PubMed
  31. Ther Adv Med Oncol. 2018 Jul 13;10:1758835918786658 - PubMed
  32. Cancer Res. 2006 Aug 15;66(16):8109-15 - PubMed
  33. Nat Struct Mol Biol. 2007 Jun;14(6):468-74 - PubMed
  34. Eur J Cancer. 2013 Nov;49(16):3547-58 - PubMed
  35. Curr Opin Chem Biol. 2021 Jun;62:24-33 - PubMed
  36. Nature. 2005 Apr 14;434(7035):917-21 - PubMed
  37. Trends Biochem Sci. 2013 Aug;38(8):386-93 - PubMed
  38. DNA Repair (Amst). 2018 Jun - Jul;66-67:24-29 - PubMed
  39. Annu Rev Med. 2015;66:455-70 - PubMed
  40. Cold Spring Harb Symp Quant Biol. 2000;65:127-33 - PubMed
  41. Curr Biol. 2009 Nov 3;19(20):1692-702 - PubMed
  42. Mol Cell. 2012 Aug 24;47(4):497-510 - PubMed
  43. Genes Dev. 1999 Oct 15;13(20):2633-8 - PubMed
  44. PLoS One. 2011;6(6):e21424 - PubMed
  45. Nat Rev Cancer. 2016 Jan;16(1):20-33 - PubMed
  46. Nat Rev Clin Oncol. 2018 Sep;15(9):564-576 - PubMed
  47. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12871-6 - PubMed
  48. J Biol Chem. 2011 Dec 9;286(49):42470-42482 - PubMed
  49. Nature. 2009 Oct 22;461(7267):1071-8 - PubMed
  50. Cell Cycle. 2011 Jun 15;10(12):1897-904 - PubMed
  51. Mol Biol Cell. 2005 Sep;16(9):4139-52 - PubMed
  52. Nucleic Acids Res. 2021 Jan 8;49(D1):D1083-D1093 - PubMed
  53. Front Cell Dev Biol. 2020 Sep 09;8:564601 - PubMed
  54. Trends Cell Biol. 2019 Sep;29(9):740-751 - PubMed
  55. Nat Protoc. 2006;1(5):2315-9 - PubMed
  56. PLoS One. 2013 Sep 05;8(9):e73710 - PubMed
  57. Cancer Discov. 2012 May;2(5):401-4 - PubMed
  58. Mol Cell Biol. 2011 Apr;31(7):1382-95 - PubMed
  59. Biochem Biophys Res Commun. 2006 Jun 23;345(1):50-8 - PubMed
  60. Signal Transduct Target Ther. 2019 Dec 24;4:64 - PubMed
  61. Nature. 2019 Jul;571(7766):576-579 - PubMed
  62. Mol Oncol. 2013 Jun;7(3):567-79 - PubMed
  63. Oncotarget. 2015 Feb 20;6(5):2779-93 - PubMed
  64. Br J Cancer. 2021 Mar;124(5):951-962 - PubMed
  65. Trends Genet. 2014 Aug;30(8):326-39 - PubMed
  66. J Hematol Oncol. 2020 Sep 3;13(1):118 - PubMed
  67. Cell Rep. 2014 Jun 12;7(5):1547-1559 - PubMed
  68. Adv Genet. 2013;82:1-45 - PubMed
  69. PLoS One. 2015 Aug 25;10(8):e0136566 - PubMed
  70. Semin Cell Dev Biol. 2021 May;113:38-46 - PubMed
  71. Mol Cell. 2010 Oct 22;40(2):179-204 - PubMed
  72. Cell. 2011 May 13;145(4):529-42 - PubMed
  73. Carcinogenesis. 2010 Jun;31(6):955-60 - PubMed
  74. Target Oncol. 2019 Dec;14(6):657-679 - PubMed
  75. Nat Rev Cancer. 2016 Feb;16(2):110-20 - PubMed
  76. Nat Rev Cancer. 2011 Jun 24;11(7):467-80 - PubMed
  77. Br J Pharmacol. 2013 Aug;169(8):1745-65 - PubMed
  78. Mol Cell Biol. 2011 Sep;31(17):3603-15 - PubMed
  79. Annu Rev Med. 2015;66:129-43 - PubMed
  80. Cell. 2020 Apr 2;181(1):102-114 - PubMed
  81. Mol Cell. 2012 Feb 10;45(3):371-83 - PubMed
  82. Clin Cancer Res. 1999 Mar;5(3):507-12 - PubMed
  83. Cell Signal. 2011 Sep;23(9):1433-40 - PubMed
  84. Carcinogenesis. 2002 May;23(5):687-96 - PubMed
  85. Int J Cancer. 2010 May 1;126(9):2079-89 - PubMed
  86. Science. 2011 Jun 10;332(6035):1313-7 - PubMed
  87. Nat Rev Clin Oncol. 2019 Feb;16(2):81-104 - PubMed

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