Synthetic lethality in DNA repair network: A novel avenue in targeted cancer therapy and combination therapeutics

IUBMB Life

Volumn 69, Issue 12, 2017, Pages 929-937

  Bhattacharjee, Sonali ^a   Nandi, Saikat ^a  

^a Simons Center for Quantitative Biology   (United States)

Author keywords

clinical trials; combination therapy; DNA double strand break repair; drug discovery; genomic instability; homologous recombination; non homologous end joining; precision medicine; synthetic lethality; targeted cancer therapy

Indexed keywords

ANTINEOPLASTIC AGENT; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; 2-(MORPHOLIN-4-YL)BENZO(H)CHROMEN-4-ONE; 6-(4-HYDROXYPHENYL)-2-THIOXO-2,3-DIHYDRO-4(1H)-PYRIMIDINONE; BENZIMIDAZOLE DERIVATIVE; CHROMONE DERIVATIVE; DNA; DOUBLE STRAND BREAK REPAIR PROTEIN MRE11; INDOLE DERIVATIVE; MORPHOLINE DERIVATIVE; MRE11A PROTEIN, HUMAN; PARP1 PROTEIN, HUMAN; PYRIMIDINONE DERIVATIVE; RUCAPARIB; THIOKETONE; VELIPARIB;

CLINICAL TRIAL; DNA END JOINING REPAIR; DNA REPAIR; DOUBLE STRANDED DNA BREAK; HOMOLOGOUS RECOMBINATION; HUMAN; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; REVIEW; SINGLE STRANDED DNA BREAK; ANTAGONISTS AND INHIBITORS; CELL CYCLE; CLINICAL TRIAL (TOPIC); DRUG EFFECT; GENETICS; LETHAL MUTATION; METABOLISM; NEOPLASM; PATHOLOGY; PROCEDURES; RECOMBINATION REPAIR;

BENZIMIDAZOLES; CELL CYCLE; CHROMONES; CLINICAL TRIALS AS TOPIC; DNA BREAKS, DOUBLE-STRANDED; DNA END-JOINING REPAIR; DNA, NEOPLASM; HUMANS; INDOLES; MOLECULAR TARGETED THERAPY; MORPHOLINES; MRE11 HOMOLOGUE PROTEIN; NEOPLASMS; POLY (ADP-RIBOSE) POLYMERASE-1; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; PYRIMIDINONES; RECOMBINATIONAL DNA REPAIR; SYNTHETIC LETHAL MUTATIONS; THIONES;

EID: 85035041094     PISSN: 15216543     EISSN: 15216551     Source Type: Journal    
DOI: 10.1002/iub.1696     Document Type: Review

References (85)

1. Bhattacharjee, S., and Nandi, S. (2016) Choices have consequences: the nexus between DNA repair pathways and genomic instability in cancer. Clin. Transl. Med. 5, 45.
2. Hori, A., Yoshida, M., Shibata, T., Ling, F. (2009) Reactive oxygen species regulate DNA copy number in isolated yeast mitochondria by triggering recombination-mediated replication. Nucl. Acids Res. 37, 749–761.
3. Symington, L. S., and Gautier, J. (2011) Double-strand break end resection and repair pathway choice. Ann. Rev. Genet. 45, 247–271.
4. Haber, J. E. (2012) Mating-type genes and MAT switching in Saccharomyces cerevisiae. Genetics 191, 33–64.
5. Soulas-Sprauel, P., Rivera-Munoz, P., Malivert, L., Le Guyader, G., Abramowski, V., et al. (2007) V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining. Oncogene 26, 7780–7791.
6. Castel, S. E., Ren, J., Bhattacharjee, S., Chang, A. Y., Sanchez, et al. (2014) Dicer promotes transcription termination at sites of replication stress to maintain genome stability. Cell 159, 572–583.
7. Dizdaroglu, M. (2015) Oxidatively induced DNA damage and its repair in cancer. Mutat. Res. Rev. Mutat Res. 763, 212–245.
8. Williams, A. B., and Schumacher, B. (2017) DNA damage responses and stress resistance: concepts from bacterial SOS to metazoan immunity. Mech. Ageing Dev. 165, 27–32.
9. Sancar, A., Lindsey-Boltz, L. A., Unsal-Kacmaz, K., Linn, S. (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Ann. Rev. Biochem. 73, 39–85.
10. Hoeijmakers, J. H. (2009) DNA damage, aging, and cancer. N. Engl. J. Med. 361, 1475–1485.
11. Hoeijmakers, J. H. (2001) Genome maintenance mechanisms for preventing cancer. Nature 411, 366–374.
12. Ciccia, A., and Elledge, S. J. (2010) The DNA damage response: making it safe to play with knives. Mol. Cell 40, 179–204.
13. Kennedy, R. D., and D'Andrea, A. D. (2006) DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes. J. Clin. Oncol. 24, 3799–3808.
14. Gavande, N. S., VanderVere-Carozza, P. S., Hinshaw, H. D., Jalal, S. I., Sears, C. R., et al. (2016) DNA repair targeted therapy: the past or future of cancer treatment? Pharmacol. Ther. 160, 65–83.
15. Caldecott, K. W. (2008) Single-strand break repair and genetic disease. Nat. Rev. Genet. 9, 619–631.
16. Barnes, D. E., and Lindahl, T. (2004) Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Ann. Rev. Genet. 38, 445–476.
17. Sugasawa, K. (2006) UV-induced ubiquitylation of XPC complex, the UV-DDB-ubiquitin ligase complex, and DNA repair. J. Mol. Histol. 37, 189–202.
18. Gillet, L. C. J., and Scharer, O. D. (2006) Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem. Rev. 106, 253–276.
19. Reyes, G. X., Schmidt, T. T., Kolodner, R. D., Hombauer, H. (2015) New insights into the mechanism of DNA mismatch repair. Chromosoma 124, 443–462.
20. Wallace, S. S. (2014) Base excision repair: a critical player in many games. DNA Repair (Amst) 19, 14–26.
21. Hanawalt, P. C., and Spivak, G. (2008) Transcription-coupled DNA repair: two decades of progress and surprises. Nat. Rev. Mol. Cell Biol. 9, 958–970.
22. Gillet, L. C., and Scharer, O. D. (2006) Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem. Rev. 106, 253–276.
23. Fagbemi, A. F., Orelli, B., and Scharer, O. D. (2011) Regulation of endonuclease activity in human nucleotide excision repair. DNA Repair 10, 722–729.
24. Kemp, M. G., Reardon, J. T., Lindsey-Boltz, L. A., Sancar, A. (2012) Mechanism of release and fate of excised oligonucleotides during nucleotide excision repair. Env. Mol. Mutagen. 53, S24–S24.
25. Shivji, M. K., Podust, V. N., Hubscher, U., Wood, R. D. (1995) Nucleotide excision-repair DNA-synthesis by DNA polymerase-epsilon in the presence of Pcna, Rfc, and Rpa. Biochemistry 34, 5011–5017.
26. Kolodner, R. D., and Marsischky, G. T. (1999) Eukaryotic DNA mismatch repair. Curr. Opin. Genet. Dev. 9, 89–96.
27. Kunkel, T. A., and Erie, D. A. (2005) DNA mismatch repair. Ann. Rev. Biochem. 74, 681–710.
28. Modrich, P., and Lahue, R. (1996) Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Ann. Rev. Biochem. 65, 101–133.
29. Li, G. M. (2008) Mechanisms and functions of DNA mismatch repair. Cell Res. 18, 85–98.
30. Nambiar, M., and Raghavan, S. C. (2011) How does DNA break during chromosomal translocations? Nucl. Acids Res. 39, 5813–5825.
31. Heyer, W. D., Ehmsen, K. T., and Liu, J. (2010) Regulation of homologous recombination in eukaryotes. Ann. Rev. Genet. 44, 113–139.
32. Shrivastav, M., De Haro, L. P., and Nickoloff, J. A. (2008) Regulation of DNA double-strand break repair pathway choice. Cell Res. 18, 134–147.
33. Mao, Z., Bozzella, M., Seluanov, A., Gorbunova, V. (2008) DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells. Cell Cycle 7, 2902–2906.
34. Davis, A. J., and Chen, D. J. (2013) DNA double strand break repair via non-homologous end-joining. Transl. Cancer Res. 2, 130–143.
35. Lieber, M. R. (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Ann. Rev. Biochem. 79, 181–211.
36. Sung, P., and Klein, H. (2006) Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat. Rev. Mol. Cell Biol. 7, 739–750.
37. Heller, R. C., and Marians, K. J. (2006) Replisome assembly and the direct restart of stalled replication forks. Nat. Rev. Mol. Cell Biol. 7, 932–943.
38. Zickler, D., and Kleckner, N. (1999) Meiotic chromosomes: integrating structure and function. Ann. Rev. Genet. 33, 603–754.
39. Mimitou, E. P., and Symington, L. S. (2008) Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature 455, 700–704.
40. Paques, F., and Haber, J. E. (1999) Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 63, 349.
41. Chen, Z., Yang, H., and Pavletich, N. P. (2008) Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structures. Nature 453, 489–484.
42. Fricke, W. M., and Brill, S. J. (2003) Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3. Genes Dev. 17, 1768–1778.
43. Gaskell, L. J., Osman, F., Gilbert, R. J., Whitby, M. C. (2007) Mus81 cleavage of Holliday junctions: a failsafe for processing meiotic recombination intermediates? EMBO J. 26, 1891–1901.
44. Ip, S. C., Rass, U., Blanco, M. G., Flynn, H. R., Skehel, J. M., et al. (2008) Identification of Holliday junction resolvases from humans and yeast. Nature 456, 357–361.
45. Lorenz, A., West, S. C., and Whitby, M. C. (2010) The human Holliday junction resolvase GEN1 rescues the meiotic phenotype of a Schizosaccharomyces pombe mus81 mutant. Nucl. Acids Res. 38, 1866–1873.
46. Wu, L., and Hickson, I. D. (2003) The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature 426, 870–874.
47. Nassif, N., Penney, J., Pal, S., Engels, W. R., Gloor, G. B. (1994) Efficient copying of nonhomologous sequences from ectopic sites via P-element-induced gap repair. Mol. Cell Biol. 14, 1613–1625.
48. Kleckner, N. (2006) Chiasma formation: chromatin/axis interplay and the role(s) of the synaptonemal complex. Chromosoma 115, 175–194.
49. Bhattacharjee, S., Osman, F., Feeney, L., Lorenz, A., Bryer, C., et al. (2013) MHF1–2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination. Open Biol. 3, 130102.
50. Nandi, S., and Whitby, M. C. (2012) The ATPase activity of Fml1 is essential for its roles in homologous recombination and DNA repair. Nucl. Acids Res. 40, 9584–9595.
51. Sun, W., Nandi, S., Osman, F., Ahn, J. S., Jakovleska, J., et al. (2008) The FANCM ortholog Fml1 promotes recombination at stalled replication forks and limits crossing over during DNA double-strand break repair. Mol. Cell 32, 118–128.
52. Barber, L. J., Youds, J. L., Ward, J. D., McIlwraith, M. J., O'Neil, N. J., et al. (2008) RTEL1 maintains genomic stability by suppressing homologous recombination. Cell 135, 261–271.
53. Dupaigne, P., Le Breton, C., Fabre, F., Gangloff, S., Le Cam, E., et al. (2008) The Srs2 helicase activity is stimulated by Rad51 filaments on dsDNA: implications for crossover incidence during mitotic recombination. Mol. Cell 29, 243–254.
54. Lorenz, A., Osman, F., Sun, W., Nandi, S., Steinacher, R., et al. (2012) The fission yeast FANCM ortholog directs non-crossover recombination during meiosis. Science 336, 1585–1588.
55. Malkova, A., and Ira, G. (2013) Break-induced replication: functions and molecular mechanism. Curr. Opin. Genet. Dev. 23, 271–279.
56. Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., et al. (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913–917.
57. Bridges, C. B. (1922) The origin of variation. Am. Nat. 56, 51–63.
58. Dobzhansky, T. (1946) Genetics of natural populations. XIII. Recombination and variability in populations of Drosphila pseudoobscura. Genetics 31, 269–290.
59. Morandell, S., and Yaffe, M. B. (2012) Exploiting synthetic lethal interactions between dna damage signaling, checkpoint control, and p53 for targeted cancer therapy. Mech. DNA Repair 110, 289–314.
60. Ooi, S. L., Pan, X., Peyser, B. D., Ye, P., Meluh, P. B., et al. (2006) Global synthetic-lethality analysis and yeast functional profiling. Trends Genet. 22, 56–63.
61. Herman-Antosiewicz, A., Xiao, H., Lew, K. L., Singh, S. V. (2007) Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line. Mol. Cancer Ther. 6, 1673–1681.
62. Sos, M. L., Fischer, S., Ullrich, R., Peifer, M., Heuckmann, J. M., et al. (2009) Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer. Proc. Natl. Acad. Sci. USA 106, 18351–18356.
63. Strom, C. E., Johansson, F., Uhlen, M., Szigyarto, C. A., Erixon, K., et al. (2011) Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediate. Nucl. Acids Res. 39, 3166–3175.
64. Fortini, P. (2003) The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie 85, 1053–1071.
65. Schreiber, V., Dantzer, F., Ame, J. C., de Murcia, G. (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat. Rev. Mol. Cell Biol. 7, 517–528.
66. Caldecott, K. W., Aoufouchi, S., Johnson, P., Shall, S. (1996) XRCC1 polypeptide interacts with DNA polymerase and possibly poly (ADP-ribose) polymerase, and DNA ligase III is a novel molecular 'nick-sensor' in vitro. Nucl. Acids Res. 24, 4387–4394.
67. Helleday, T. (2011) The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol. Oncol. 5, 387–393.
68. Plummer, R., Jones, C., Middleton, M., Wilson, R., Evans, J., et al. (2008) Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors. Clin. Cancer Res. 14, 7917–7923.
69. Plummer, R., Lorigan, P., Steven, N., Scott, L., Middleton, M. R., et al. (2013) A phase II study of the potent PARP inhibitor, Rucaparib (PF-01367338, AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of chemopotentiation. Cancer Chemother. Pharmacol. 71, 1191–1199.
70. Mehta, M. P., Wang, D., Wang, F., Kleinberg, L., Brade, A., et al. (2015) Veliparib in combination with whole brain radiation therapy in patients with brain metastases: results of a phase 1 study. J. Neurooncol. 122, 409–417.
71. Fong, P. C., Yap, T. A., Boss, D. S., Carden, C. P., Mergui-Roelvink, M., et al. (2010) Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J. Clin. Oncol. 28, 2512–2519.
72. Gubin, M. M., Artyomov, M. N., Mardis, E. R., Schreiber, R. D., et al. (2015) Tumor neoantigens: building a framework for personalized cancer immunotherapy. J. Clin. Invest. 125, 3413–3421.
73. Dupre, A., Boyer-Chatenet, L., Sattler, R. M., Modi, A. P., Lee, J. H., et al. (2008) A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex. Nat. Chem. Biol. 4, 119–125.
74. Zhou, Y., and Paull, T. T. (2013) DNA-dependent protein kinase regulates DNA end resection in concert with Mre11-Rad50-Nbs1 (MRN) and ataxia telangiectasia-mutated (ATM). J. Biol. Chem. 288, 37112–37125.
75. Huang, F., and Mazin, A. V. (2014) A small molecule inhibitor of human RAD51 potentiates breast cancer cell killing by therapeutic agents in mouse xenografts. PLoS One 9, e100993.
76. Peasland, A., Wang, L. Z., Rowling, E., Kyle, S., Chen, T., et al. (2011) Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br. J. Cancer 105, 372–381.
77. Hickson, I., Yan, Z., Richardson, C. J., Green, S. J., Martin, N. M. B., et al. (2004) Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res. 64, 9152–9159.
78. Rainey, M. D., Charlton, M. E., Stanton, R. V., Kastan, M. B., et al. (2008) Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res. 68, 7466–7474.
79. Golding, S. E., Rosenberg, E., Valerie, N., Hussaini, I., Frigerio, M., et al. (2009) Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol. Cancer Therapeut. 8, 2894–2902.
80. Bhattacharjee, S., and Nandi, S. (2017) DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway. Cell Commun. Signal. 15, 41.
81. Morgan, M. A., Parsels, L. A., Zhao, L., Parsels, J. D., Davis, M. A., et al. (2010) Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Res. 70, 4972–4981.
82. Sullivan, K., Cramer-Morales K., McElroy, D. L., Ostrov, D. A., Haas, K., et al. (2016) Identification of a small molecule inhibitor of RAD52 by structure-based selection. PLoS One 11, e0147230.
83. Chandramouly, G., McDevitt, S., Sullivan, K., Kent, T., Luz, A., et al. (2015) Small-molecule disruption of RAD52 rings as a mechanism for precision medicine in BRCA-deficient cancers. Chem. Biol. 22, 1491–1504.
84. Willmore, E., de Caux, S., Sunter, N. J., Tilby, M. J., Jackson, G. H., et al. (2004) A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. Blood 103, 4659–4665.
85. Srivastava, M., Nambiar, M., Sharma, S., Karki, S. S., Goldsmith, G., et al. (2012) An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell 151, 1474–1487.