Skip to main content
SpringerLink
Log in

Repair of DNA Interstrand Cross-links Produced by Cancer Chemotherapeutic Drugs

  • Chapter
  • First Online:
Advances in DNA Repair in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D,volume 72))

  • 1275 Accesses

Abstract

It has been clear for over 50 years that bifunctional reactivity is an essential prerequisite for the potent cytotoxic and antitumour activity of agents such as the nitrogen mustards [1]. DNA was later identified as a target for these drugs [2, 3], and the covalent modification of DNA almost certainly accounts for the antitumour activity of these drugs [1]. The fact that a bifunctional covalent reaction with DNA (cross-linking) is essential for the toxicity of these agents is evident from studies employing monofunctional analogues; for drugs such as the nitrogen mustards mechlorethamine and melphalan, their monofunctional counterparts are many orders of magnitude less toxic [4, 5]. Cross links can be formed on the same strand of DNA (intrastrand), between the two complementary strands of DNA (interstrand), or between a base on DNA and a reactive group on a protein (DNA–protein). For the bifunctional alkylating drugs (e.g. the nitrogen mustard class and mitoycin C), it is clear that the interstrand cross link (ICL), although accounting for only a small proportion of the total DNA adducts, is the critical cytotoxic lesion [6, 7]. For the platinum drugs (e.g. cisplatin and carboplatin) the majority (>80 %) of DNA adducts are intrastrand cross-links, although the <5 % of ICLs are critical cytotoxic lesions [8].

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Hartley JA (2001) Alkylating agents. In: Souhami RL, Tannock RF, Hohenberger P, Horiot J-C (eds) Oxford textbook of oncology, vol 1. Oxford University Press, Oxford, pp 639–654

    Google Scholar 

  2. Kohn KW, Spears CL et al (1966) Inter-strand crosslinking of DNA by nitrogen mustard. J Mol Biol 19(2):266–288

    Article  PubMed  CAS  Google Scholar 

  3. Lawley PD, Brookes P (1967) Interstrand crosslinking of DNA by difunctional alkylating agents. J Mol Biol 25:143–160

    Article  PubMed  CAS  Google Scholar 

  4. Clingen PH, De Silva IU et al (2005) The XPF-ERCC1 endonuclease and homologous recombination contribute to the repair of minor groove DNA interstrand crosslinks in mammalian cells produced by the pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136. Nucleic Acids Res 33(10):3283–3291

    Article  PubMed  CAS  Google Scholar 

  5. De Silva IU, McHugh PJ et al (2000) Defining the roles of nucleotide excision repair and recombination in the repair of DNA interstrand cross-links in mammalian cells. Mol Cell Biol 20(21):7980–7990

    Article  PubMed  Google Scholar 

  6. O’Connor PM, Kohn KW (1990) Comparative pharmacokinetics of DNA lesion formation and removal following treatment of L1210 cells with nitrogen mustards. Cancer Commun 2(12):387–394

    PubMed  Google Scholar 

  7. Sunters A, Springer CJ et al (1992) The cytotoxicity, DNA crosslinking ability and DNA sequence selectivity of the aniline mustards melphalan, chlorambucil and 4-[bis(2-chloroethyl)amino] benzoic acid. Biochem Pharmacol 44(1):59–64

    Article  PubMed  CAS  Google Scholar 

  8. Trimmer EE, Essigmann JM (1999) Cisplatin. Essays Biochem 34:191–211

    PubMed  CAS  Google Scholar 

  9. Osawa T, Davies D et al (2011) Mechanism of cell death resulting from DNA interstrand cross-linking in mammalian cells. Cell Death Dis 2:e187

    Article  PubMed  CAS  Google Scholar 

  10. Koberle B, Masters JR et al (1999) Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours. Curr Biol 9(5):273–276

    Article  PubMed  CAS  Google Scholar 

  11. Spanswick VJ, Craddock C et al (2002) Repair of DNA interstrand crosslinks as a mechanism of clinical resistance to melphalan in multiple myeloma. Blood 100(1):224–229

    Article  PubMed  CAS  Google Scholar 

  12. Torres-Garcia SJ, Cousineau L et al (1989) Correlation of resistance to nitrogen mustards in chronic lymphocytic leukemia with enhanced removal of melphalan-induced DNA cross-links. Biochem Pharmacol 38(18):3122–3123

    Article  PubMed  CAS  Google Scholar 

  13. Wynne P, Newton C et al (2007) Enhanced repair of DNA interstrand crosslinking in ovarian cancer cells from patients following treatment with platinum-based chemotherapy. Br J Cancer 97(7):927–933

    PubMed  CAS  Google Scholar 

  14. Rudd GN, Hartley JA, Souhami RL (1995) Persistence of cisplatin-induced DNA interstrand crosslinks in peripheral blood mononuclear cells from elderly and young individuals. Cancer Chemother Pharmacol 35:323–326

    Article  PubMed  CAS  Google Scholar 

  15. Ojwang JO, Grueneberg DA et al (1989) Synthesis of a duplex oligonucleotide containing a nitrogen mustard interstrand DNA-DNA cross-link. Cancer Res 49(23):6529–6537

    PubMed  CAS  Google Scholar 

  16. Huang H, Zhu L et al (1995) Solution structure of a cisplatin-induced DNA interstrand cross-link. Science 270(5243):1842–1845

    Article  PubMed  CAS  Google Scholar 

  17. Tomasz M (1995) Mitomycin C: small, fast and deadly (but very selective). Chem Biol 2(9):575–579

    Article  PubMed  CAS  Google Scholar 

  18. Ben-Hur E, Song PS (1984) The photochemistry and photobiology of furocoumarins (psoralens). Adv Radiat Biol 11:131–171

    CAS  Google Scholar 

  19. Rink SM, Hopkins PB (1995) A mechlorethamine-induced DNA interstrand cross-link bends duplex DNA. Biochemistry 34(4):1439–1445

    Article  PubMed  CAS  Google Scholar 

  20. Hartley JA (2011) The development of pyrrolobenzodiazepines as antitumour agents. Expert Opin Investig Drugs 20(6):733–744

    Article  PubMed  CAS  Google Scholar 

  21. Hartley JA, Spanswick VJ et al (2004) SJG-136 (NSC 694501), a novel rationally designed DNA minor groove interstrand cross-linking agent with potent and broad spectrum antitumor activity: part 1: cellular pharmacology, in vitro and initial in vivo antitumor activity. Cancer Res 64(18):6693–6699

    Article  PubMed  CAS  Google Scholar 

  22. Kiakos K, Hartley JM et al (2010) Measurement of DNA interstrand crosslinking in naked DNA using gel-based methods. Methods Mol Biol 613:283–302

    Article  PubMed  CAS  Google Scholar 

  23. Wang AT, Sengerova B et al (2011) Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair. Genes Dev 25(17):1859–1870

    Article  PubMed  CAS  Google Scholar 

  24. Cole RS (1973) Repair of DNA containing interstrand crosslinks in Escherichia coli: sequential excision and recombination. Proc Natl Acad Sci USA 70(4):1064–1068

    Article  PubMed  CAS  Google Scholar 

  25. McHugh PJ, Spanswick VJ et al (2001) Repair of DNA interstrand crosslinks: molecular mechanisms and clinical relevance. Lancet Oncol 2(8):483–490

    Article  PubMed  CAS  Google Scholar 

  26. Berardini M, Mackay W et al (1997) Evidence for a recombination-independent pathway for the repair of DNA interstrand cross-links based on a site-specific study with nitrogen mustard. Biochemistry 36(12):3506–3513

    Article  PubMed  CAS  Google Scholar 

  27. Cole RS (1971) Inactivation of Escherichia coli, F’ episomes at transfer, and bacteriophage lambda by psoralen plus 360-nm light: significance of deoxyribonucleic acid cross-links. J Bacteriol 107(3):846–852

    PubMed  CAS  Google Scholar 

  28. Henriques JA, Moustacchi E (1980) Isolation and characterization of pso mutants sensitive to photo-addition of psoralen derivatives in Saccharomyces cerevisiae. Genetics 95(2):273–288

    PubMed  CAS  Google Scholar 

  29. Lawley PD, Brookes P (1965) Molecular mechanism of the cytotoxic action of difunctional alkylating agents and of resistance to this action. Nature 206(983):480–483

    Article  PubMed  CAS  Google Scholar 

  30. Berardini M, Foster PL et al (1999) DNA polymerase II (polB) is involved in a new DNA repair pathway for DNA interstrand cross-links in Escherichia coli. J Bacteriol 181(9):2878–2882

    PubMed  CAS  Google Scholar 

  31. Kumari A, Minko IG et al (2008) Replication bypass of interstrand cross-link intermediates by Escherichia coli DNA polymerase IV. J Biol Chem 283(41):27433–27437

    Article  PubMed  CAS  Google Scholar 

  32. Munn M, Rupp W (1991) Interaction of the UvrABC endonuclease with DNA containing a psoralen monoadduct or cross-link. Differential effects of superhelical density and comparison of preincision complexes. J Biol Chem 266(36):24748–24756

    PubMed  CAS  Google Scholar 

  33. Pu WT, Kahn R et al (1989) UvrABC incision of N-methylmitomycin A-DNA monoadducts and cross-links. J Biol Chem 264(34):20697–20704

    PubMed  CAS  Google Scholar 

  34. Sladek F, Munn M et al (1989) In vitro repair of psoralen-DNA cross-links by RecA, UvrABC, and the 5′- exonuclease of DNA polymerase I. J Biol Chem 264(12):6755–6765

    PubMed  CAS  Google Scholar 

  35. Van Houten B, Gamper H et al (1986) Action mechanism of ABC excision nuclease on a DNA substrate containing a psoralen crosslink at a defined position. Proc Natl Acad Sci USA 83(21):8077–8081

    Article  PubMed  Google Scholar 

  36. Zietlow L, Bessho T (2008) DNA polymerase I-mediated translesion synthesis in RecA-independent DNA interstrand cross-link repair in E. coli. Biochemistry 47(19):5460–5464

    Article  PubMed  CAS  Google Scholar 

  37. Smeaton MB, Hlavin EM et al (2008) Distortion-dependent unhooking of interstrand cross-links in mammalian cell extracts. Biochemistry 47(37):9920–9930

    Article  PubMed  CAS  Google Scholar 

  38. Clement FC, Camenisch U et al (2010) Dynamic two-stage mechanism of versatile DNA damage recognition by xeroderma pigmentosum group C protein. Mutat Res 685(1–2):21–28

    PubMed  CAS  Google Scholar 

  39. Thoma BS, Wakasugi M et al (2005) Human XPC-hHR23B interacts with XPA-RPA in the recognition of triplex-directed psoralen DNA interstrand crosslinks. Nucleic Acids Res 33(9):2993–3001

    Article  PubMed  CAS  Google Scholar 

  40. Muniandy PA, Thapa D et al (2009) Repair of laser-localized DNA interstrand cross-links in G1 phase mammalian cells. J Biol Chem 284(41):27908–27917

    Article  PubMed  CAS  Google Scholar 

  41. Furuta T, Ueda T et al (2002) Transcription-coupled nucleotide excision repair as a determinant of cisplatin sensitivity of human cells. Cancer Res 62(17):4899–4902

    PubMed  CAS  Google Scholar 

  42. Lange SS, Reddy MC, Vasquez KM (2009) Human HMGB1 directly facilitates interactions between nucleotide excision repair proteins on triplex-directed psoralen interstrand crosslinks DNA Repair (Amst) 8:865–872

    Google Scholar 

  43. Hlavin EM, Smeaton MB et al (2010) Initiation of DNA interstrand cross-link repair in mammalian cells. Environ Mol Mutagen 51(6):604–624

    PubMed  CAS  Google Scholar 

  44. Futscher BW, Pieper RO et al (1992) DNA-damaging and transcription-terminating lesions induced by AF64A in vitro. J Neurochem 58(4):1504–1509

    Article  PubMed  CAS  Google Scholar 

  45. Islas AL, Vos JM et al (1991) Differential introduction and repair of psoralen photoadducts to DNA in specific human genes. Cancer Res 51(11):2867–2873

    PubMed  CAS  Google Scholar 

  46. Larminat F, Bohr VA (1994) Role of the human ERCC-1 gene in gene-specific repair of cisplatin-induced DNA damage. Nucleic Acids Res 22(15):3005–3010

    Article  PubMed  CAS  Google Scholar 

  47. Ahn B, Kang D et al (2004) Repair of mitomycin C cross-linked DNA in mammalian cells measured by a host cell reactivation assay. Mol Cells 18(2):249–255

    PubMed  CAS  Google Scholar 

  48. Wang G, Chen Z et al (2001) Detection and determination of oligonucleotide triplex formation-mediated transcription-coupled DNA repair in HeLa nuclear extracts. Nucleic Acids Res 29(8):1801–1807

    Article  PubMed  CAS  Google Scholar 

  49. Zheng H, Wang X et al (2003) Nucleotide excision repair- and polymerase eta-mediated error-prone removal of mitomycin C interstrand cross-links. Mol Cell Biol 23(2):754–761

    Article  PubMed  CAS  Google Scholar 

  50. Dronkert ML, Kanaar R (2001) Repair of DNA interstrand cross-links. Mutat Res 486:217–247

    Article  PubMed  CAS  Google Scholar 

  51. Niedernhofer LJ, Lalai AS et al (2005) Fanconi anemia (cross)linked to DNA repair. Cell 123(7):1191–1198

    Article  PubMed  CAS  Google Scholar 

  52. Patel KJ, Joenje H (2007) Fanconi anemia and DNA replication repair. DNA Repair (Amst) 6(7):885–890

    Article  CAS  Google Scholar 

  53. Thompson LH, Hinz JM (2009) Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights. Mutat Res 668(1–2):54–72

    PubMed  CAS  Google Scholar 

  54. Akkari YMN, Bateman RL et al (2000) DNA replication is required to elicit cellular responses to psoralen-induced DNA interstrand cross-links. Mol Cell Biol 20(21):8283–8289

    Article  PubMed  CAS  Google Scholar 

  55. McHugh PJ, Sones WR et al (2000) Repair of intermediate structures produced at DNA interstrand cross-links in Saccharomyces cerevisiae. Mol Cell Biol 20(10):3425–3433

    Article  PubMed  CAS  Google Scholar 

  56. Knipscheer P, Raschle M et al (2009) The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. Science 326(5960):1698–1701

    Article  PubMed  CAS  Google Scholar 

  57. Räschle M, Knipscheer P et al (2008) Mechanism of replication-coupled DNA interstrand crosslink repair. Cell 134(6):969–980

    Article  PubMed  CAS  Google Scholar 

  58. Ben-Yehoyada M, Wang LC et al (2009) Checkpoint signaling from a single DNA interstrand crosslink. Mol Cell 35(5):704–715

    Article  PubMed  CAS  Google Scholar 

  59. Lambert S, Froget B et al (2007) Arrested replication fork processing: interplay between checkpoints and recombination. DNA Repair 6(7):1042–1061

    Article  PubMed  CAS  Google Scholar 

  60. Andersson BS, Sadeghi T et al (1996) Nucleotide excision repair genes as determinants of cellular sensitivity to cyclophosphamide analogs. Cancer Chemother Pharmacol 38(5):406–416

    Article  PubMed  CAS  Google Scholar 

  61. Hoy CA, Thompson LH et al (1985) Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents. Cancer Res 45(4):1737–1743

    PubMed  CAS  Google Scholar 

  62. Niedernhofer LJ (2004) The structure-specific endonuclease Ercc1-Xpf is required to resolve DNA interstrand cross-link-induced double-strand breaks. Mol Cell Biol 24:5776–5787

    Article  PubMed  CAS  Google Scholar 

  63. Kuraoka I, Kobertz WR et al (2000) Repair of an interstrand DNA cross-link initiated by ERCC1-XPF repair/recombination nuclease. J Biol Chem 275(34):26632–26636

    Article  PubMed  CAS  Google Scholar 

  64. Abraham J, Lemmers B et al (2003) Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells. EMBO J 22(22):6137–6147

    Article  PubMed  CAS  Google Scholar 

  65. Hanada K, Budzowska M et al (2006) The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks. EMBO J 25(20):4921–4932

    Article  PubMed  CAS  Google Scholar 

  66. Bhagwat N, Olsen AL et al (2009) XPF-ERCC1 participates in the Fanconi anemia pathway of cross-link repair. Mol Cell Biol 29(24):6427–6437

    Article  PubMed  CAS  Google Scholar 

  67. Andersen SL, Bergstralh DT et al (2009) Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombination. Mol Cell 35(1):128–135

    Article  PubMed  CAS  Google Scholar 

  68. Fekairi S, Scaglione S et al (2009) Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell 138(1):78–89

    Article  PubMed  CAS  Google Scholar 

  69. Muñoz IM, Hain K et al (2009) Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. Mol Cell 35(1):116–127

    Article  PubMed  CAS  Google Scholar 

  70. Svendsen JM, Smogorzewska A et al (2009) Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell 138(1):63–77

    Article  PubMed  CAS  Google Scholar 

  71. Cannavo E, Gerrits B et al (2007) Characterization of the interactome of the human MutL homologues MLH1, PMS1, and PMS2. J Biol Chem 282(5):2976–2986

    Article  PubMed  CAS  Google Scholar 

  72. Kratz K, Schopf B et al (2010) Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell 142(1):77–88

    Article  PubMed  CAS  Google Scholar 

  73. MacKay C, Declais AC et al (2010) Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2. Cell 142(1):65–76

    Article  PubMed  CAS  Google Scholar 

  74. Smogorzewska A, Desetty R et al (2010) A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair. Mol Cell 39(1):36–47

    Article  PubMed  CAS  Google Scholar 

  75. Ho TV, Scharer OD (2010) Translesion DNA synthesis polymerases in DNA interstrand crosslink repair. Environ Mol Mutagen 51(6):552–566

    PubMed  CAS  Google Scholar 

  76. Minko IG, Harbut MB et al (2008) Role for DNA polymerase kappa in the processing of N2-N2-guanine interstrand cross-links. J Biol Chem 283(25):17075–17082

    Article  PubMed  CAS  Google Scholar 

  77. Henriques JA, Moustacchi E (1981) Interactions between mutations for sensitivity to psoralen photoaddition (pso) and to radiation (rad) in Saccharomyces cerevisiae. J Bacteriol 148(1):248–256

    PubMed  CAS  Google Scholar 

  78. Ruhland A, Kircher M et al (1981) A yeast mutant specifically sensitive to bifunctional alkylation. Mutat Res 91(6):457–462

    Article  PubMed  CAS  Google Scholar 

  79. Demuth I, Bradshaw PS et al (2008) Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation. DNA Repair (Amst) 7(8):1192–1201

    Article  CAS  Google Scholar 

  80. Dronkert MLG, de Wit J et al (2000) Disruption of mouse SNM1 causes increased sensitivity to the DNA interstrand cross-linking agent mitomycin C. Mol Cell Biol 20(13):4553–4561

    Article  PubMed  CAS  Google Scholar 

  81. Moshous D, Callebaut I et al (2001) Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell 105(2):177–186

    Article  PubMed  CAS  Google Scholar 

  82. Cattell E, Sengerova B et al (2010) The SNM1/Pso2 family of ICL repair nucleases: from yeast to man. Environ Mol Mutagen 51(6):635–645

    PubMed  CAS  Google Scholar 

  83. Hazrati A, Ramis-Castelltort M et al (2008) Human SNM1A suppresses the DNA repair defects of yeast pso2 mutants. DNA Repair (Amst) 7(2):230–238

    Article  CAS  Google Scholar 

  84. Hejna J, Philip S et al (2007) The hSNM1 protein is a DNA 5′-exonuclease. Nucleic Acids Res 35(18):6115–6123

    Article  PubMed  CAS  Google Scholar 

  85. Yang K, Moldovan GL et al (2010) RAD18-dependent recruitment of SNM1A to DNA repair complexes by a ubiquitin-binding zinc finger. J Biol Chem 285(25):19085–19091

    Article  PubMed  CAS  Google Scholar 

  86. Kannouche P, Fernandez de Henestrosa AR et al (2003) Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells. EMBO J 22(5):1223–1233

    PubMed  CAS  Google Scholar 

  87. Kannouche PL, Wing J et al (2004) Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Mol Cell 14(4):491–500

    Article  PubMed  CAS  Google Scholar 

  88. Nojima K, Hochegger H et al (2005) Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells. Cancer Res 65(24):11704–11711

    Article  PubMed  CAS  Google Scholar 

  89. Gan GN, Wittschieben JP et al (2008) DNA polymerase zeta (pol zeta) in higher eukaryotes. Cell Res 18(1):174–183

    Article  PubMed  CAS  Google Scholar 

  90. Sonoda E, Okada T et al (2003) Multiple roles of Rev3, the catalytic subunit of polzeta in maintaining genome stability in vertebrates. EMBO J 22(12):3188–3197

    Article  PubMed  CAS  Google Scholar 

  91. Okada T, Sonoda E et al (2005) Multiple roles of vertebrate REV genes in DNA repair and recombination. Mol Cell Biol 25(14):6103–6111

    Article  PubMed  CAS  Google Scholar 

  92. Ross A-L, Simpson LJ et al (2005) Vertebrate DNA damage tolerance requires the C-terminus but not BRCT or transferase domains of REV1. Nucleic Acids Res 33(4):1280–1289

    Article  PubMed  CAS  Google Scholar 

  93. Shen X, Jun S et al (2006) REV3 and REV1 play major roles in recombination-independent repair of DNA interstrand cross-links mediated by monoubiquitinated proliferating cell nuclear antigen (PCNA). J Biol Chem 281(20):13869–13872

    Article  PubMed  CAS  Google Scholar 

  94. Albertella MR, Green CM et al (2005) A role for polymerase η in the cellular tolerance to cisplatin-induced damage. Cancer Res 65(21):9799–9806

    Article  PubMed  CAS  Google Scholar 

  95. Moldovan GL, Madhavan MV et al (2010) DNA polymerase POLN participates in cross-link repair and homologous recombination. Mol Cell Biol 30(4):1088–1096

    Article  PubMed  CAS  Google Scholar 

  96. Yamanaka K, Minko IG et al (2010) Novel enzymatic function of DNA polymerase nu in translesion DNA synthesis past major groove DNA-peptide and DNA-DNA cross-links. Chem Res Toxicol 23(3):689–695

    Article  PubMed  CAS  Google Scholar 

  97. Zietlow L, Smith LA et al (2009) Evidence for the involvement of human DNA polymerase N in the repair of DNA interstrand cross-links. Biochemistry 48(49):11817–11824

    Article  PubMed  CAS  Google Scholar 

  98. Ho TV, Guainazzi A et al (2011) Structure-dependent bypass of DNA interstrand crosslinks by translesion synthesis polymerases. Nucleic Acids Res 39(17):7455–7464

    Article  PubMed  CAS  Google Scholar 

  99. Jones NJ, Stewart SA et al (1990) Biochemical and genetic analysis of the Chinese hamster mutants irs1 and irs2 and their comparison to cultured ataxia telangiectasia cells. Mutagenesis 5(1):15–23

    Article  PubMed  CAS  Google Scholar 

  100. Takata M, Sasaki MS et al (2001) Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs. Mol Cell Biol 21(8):2858–2866

    Article  PubMed  CAS  Google Scholar 

  101. Takata M, Sasaki MS et al (1998) Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J 17(18):5497–5508

    Article  PubMed  CAS  Google Scholar 

  102. Wesoly J, Agarwal S et al (2006) Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis. Mol Cell Biol 26(3):976–989

    Article  PubMed  CAS  Google Scholar 

  103. Bhattacharyya A, Ear US et al (2000) The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J Biol Chem 275(31):23899–23903

    Article  PubMed  CAS  Google Scholar 

  104. Wiegant WW, Overmeer RM et al (2006) Chinese hamster cell mutant, V-C8, a model for analysis of Brca2 function. Mutat Res 600(1–2):79–88

    PubMed  CAS  Google Scholar 

  105. Yu VP, Koehler M et al (2000) Gross chromosomal rearrangements and genetic exchange between nonhomologous chromosomes following BRCA2 inactivation. Genes Dev 14(11):1400–1406

    PubMed  CAS  Google Scholar 

  106. Long DT, Raschle M et al (2011) Mechanism of RAD51-dependent DNA interstrand cross-link repair. Science 333(6038):84–87

    Article  PubMed  CAS  Google Scholar 

  107. Bodell WJ (1990) Molecular dosimetry for sister-chromatid exchange induction and cytotoxicity by monofunctional and bifunctional alkylating agents. Mutat Res 233(1–2):203–210

    PubMed  CAS  Google Scholar 

  108. Liu Y, Nairn RS et al (2008) Processing of triplex-directed psoralen DNA interstrand crosslinks by recombination mechanisms. Nucleic Acids Res 36(14):4680–4688

    Article  PubMed  CAS  Google Scholar 

  109. Fishman-Lobell J, Haber JE (1992) Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science 258(5081):480–484

    Article  PubMed  CAS  Google Scholar 

  110. Ahmad A, Robinson AR et al (2008) ERCC1-XPF endonuclease facilitates DNA double-strand break repair. Mol Cell Biol 28(16):5082–5092

    Article  PubMed  CAS  Google Scholar 

  111. Adair GM, Rolig RL et al (2000) Role of ERCC1 in removal of long non-homologous tails during targeted homologous recombination. EMBO J 19(20):5552–5561

    Article  PubMed  CAS  Google Scholar 

  112. Sargent RG, Meservy JL et al (2000) Role of the nucleotide excision repair gene ERCC1 in formation of recombination-dependent rearrangements in mammalian cells. Nucleic Acids Res 28(19):3771–3778

    Article  PubMed  CAS  Google Scholar 

  113. Sargent RG, Rolig RL et al (1997) Recombination-dependent deletion formation in mammalian cells deficient in the nucleotide excision repair gene ERCC1. Proc Natl Acad Sci USA 94(24):13122–13127

    Article  PubMed  CAS  Google Scholar 

  114. Zhang N, Liu X et al (2007) Double-strand breaks induce homologous recombinational repair of interstrand cross-links via cooperation of MSH2, ERCC1-XPF, REV3, and the Fanconi anemia pathway. DNA Repair (Amst) 6(11):1670–1678

    Article  CAS  Google Scholar 

  115. Al-Minawi AZ, Lee Y-F et al (2009) The ERCC1/XPF endonuclease is required for completion of homologous recombination at DNA replication forks stalled by inter-strand cross-links. Nucleic Acids Res 37(19):6400–6413

    Article  PubMed  CAS  Google Scholar 

  116. Kee Y, D’Andrea AD (2010) Expanded roles of the Fanconi anemia pathway in preserving genomic stability. Genes Dev 24(16):1680–1694

    Article  PubMed  CAS  Google Scholar 

  117. Meetei AR, Levitus M et al (2004) X-linked inheritance of Fanconi anemia complementation group B. Nat Genet 36(11):1219–1224

    Article  PubMed  CAS  Google Scholar 

  118. Kennedy RD, D’Andrea AD (2006) DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes. J Clin Oncol 24(23):3799–3808

    Article  PubMed  CAS  Google Scholar 

  119. Wang LC, Gautier J (2010) The Fanconi anemia pathway and ICL repair: implications for cancer therapy. Crit Rev Biochem Mol Biol 45(5):424–439

    Article  PubMed  CAS  Google Scholar 

  120. Garcia-Higuera I, Taniguchi T et al (2001) Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Mol Cell 7(2):249–262

    Article  PubMed  CAS  Google Scholar 

  121. Smogorzewska A, Matsuoka S et al (2007) Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair. Cell 129(2):289–301

    Article  PubMed  CAS  Google Scholar 

  122. Meetei AR, Yan Z et al (2004) FANCL replaces BRCA1 as the likely ubiquitin ligase responsible for FANCD2 monoubiquitination. Cell Cycle 3(2):179–181

    Article  PubMed  CAS  Google Scholar 

  123. Kim JM, Kee Y et al (2008) Cell cycle-dependent chromatin loading of the Fanconi anemia core complex by FANCM/FAAP24. Blood 111(10):5215–5222

    Article  PubMed  CAS  Google Scholar 

  124. Moldovan G-L, D’Andrea AD (2009) How the Fanconi anemia pathway guards the genome. Annu Rev Genet 43(1):223–249

    Article  PubMed  CAS  Google Scholar 

  125. Crossan GP, van der Weyden L et al (2011) Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia. Nat Genet 43(2):147–152

    Article  PubMed  CAS  Google Scholar 

  126. Kim Y, Lach FP et al (2011) Mutations of the SLX4 gene in Fanconi anemia. Nat Genet 43(2):142–146

    Article  PubMed  CAS  Google Scholar 

  127. Stoepker C, Hain K et al (2011) SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype. Nat Genet 43(2):138–141

    Article  PubMed  CAS  Google Scholar 

  128. Cohn MA, Kowal P et al (2007) A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway. Mol Cell 28(5):786–797

    Article  PubMed  CAS  Google Scholar 

  129. Nijman SM, Huang TT et al (2005) The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Mol Cell 17(3):331–339

    Article  PubMed  CAS  Google Scholar 

  130. Kim JM, Parmar K et al (2009) Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype. Dev Cell 16(2):314–320

    Article  PubMed  CAS  Google Scholar 

  131. McMahon LW, Sangerman J et al (2001) Human α spectrin II and the FANCA, FANCC, and FANCG proteins bind to DNA containing psoralen interstrand cross-links‚ Ć. Biochemistry 40(24):7025–7034

    Article  PubMed  CAS  Google Scholar 

  132. Shen X, Do H et al (2009) Recruitment of fanconi anemia and breast cancer proteins to DNA damage sites is differentially governed by replication. Mol Cell 35(5):716–723

    Article  PubMed  CAS  Google Scholar 

  133. Liu T, Ghosal G et al (2010) FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair. Science 329(5992):693–696

    Article  PubMed  CAS  Google Scholar 

  134. Auerbach AD, Wolman SR (1976) Susceptibility of Fanconi’s anaemia fibroblasts to chromosome damage by carcinogens. Nature 261(5560):494–496

    Article  PubMed  CAS  Google Scholar 

  135. Adamo A, Collis SJ et al (2010) Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. Mol Cell 39(1):25–35

    Article  PubMed  CAS  Google Scholar 

  136. Pace P, Mosedale G et al (2010) Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway. Science 329(5988):219–223

    Article  PubMed  CAS  Google Scholar 

  137. Cipak L, Watanabe N et al (2006) The role of BRCA2 in replication-coupled DNA interstrand cross-link repair in vitro. Nat Struct Mol Biol 13(8):729–733

    Article  PubMed  CAS  Google Scholar 

  138. Hussain S, Wilson JB et al (2004) Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. Hum Mol Genet 13(12):1241–1248

    Article  PubMed  CAS  Google Scholar 

  139. Taniguchi T, Garcia-Higuera I et al (2002) S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. Blood 100(7):2414–2420

    Article  PubMed  CAS  Google Scholar 

  140. Wang X, Andreassen PR et al (2004) Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Mol Cell Biol 24(13):5850–5862

    Article  PubMed  CAS  Google Scholar 

  141. Wilson JB, Yamamoto K et al (2008) FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3. Oncogene 27(26):3641–3652

    Article  PubMed  CAS  Google Scholar 

  142. Nakanishi K, Taniguchi T et al (2002) Interaction of FANCD2 and NBS1 in the DNA damage response. Nat Cell Biol 4(12):913–920

    Article  PubMed  CAS  Google Scholar 

  143. Roques C, Coulombe Y et al (2009) MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair. EMBO J 28(16):2400–2413

    Article  PubMed  CAS  Google Scholar 

  144. Andreassen PR, D’Andrea AD et al (2004) ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes Dev 18(16):1958–1963

    Article  PubMed  CAS  Google Scholar 

  145. Zhi G, Wilson JB et al (2009) Fanconi anemia complementation group FANCD2 protein serine 331 phosphorylation is important for fanconi anemia pathway function and BRCA2 interaction. Cancer Res 69(22):8775–8783

    Article  PubMed  CAS  Google Scholar 

  146. Spanswick VJ, Hartley JM et al (2010) Measurement of DNA interstrand crosslinking in individual cells using the Single Cell Gel Electrophoresis (Comet) assay. Methods Mol Biol 613:267–282

    Article  PubMed  CAS  Google Scholar 

  147. Taniguchi T, Tischkowitz M et al (2003) Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 9(5):568–574

    Article  PubMed  CAS  Google Scholar 

  148. Reinhardt HC, Aslanian AS et al (2007) p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell 11(2):175–189

    Article  PubMed  CAS  Google Scholar 

  149. Koniaras K, Cuddihy AR et al (2001) Inhibition of Chk1-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells. Oncogene 20(51):7453–7463

    Article  PubMed  CAS  Google Scholar 

  150. Bergman AM, Ruiz van Haperen VW et al (1996) Synergistic interaction between cisplatin and gemcitabine in vitro. Clin Cancer Res 2(3):521–530

    PubMed  CAS  Google Scholar 

  151. Ledermann JA, Gabra H et al (2010) Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer. Clin Cancer Res 16(19):4899–4905

    Article  PubMed  CAS  Google Scholar 

  152. Corrie PG, Shaw J et al (2005) Phase I trial combining gemcitabine and treosulfan in advanced cutaneous and uveal melanoma patients. Br J Cancer 92(11):1997–2003

    Article  PubMed  CAS  Google Scholar 

  153. Li L, Keating MJ et al (1997) Fludarabine-mediated repair inhibition of cisplatin-induced DNA lesions in human chronic myelogenous leukemia-blast crisis K562 cells: induction of synergistic cytotoxicity independent of reversal of apoptosis resistance. Mol Pharmacol 52(5):798–806

    PubMed  CAS  Google Scholar 

  154. Moufarij MA, Sampath D et al (2006) Fludarabine increases oxaliplatin cytotoxicity in normal and chronic lymphocytic leukemia lymphocytes by suppressing interstrand DNA crosslink removal. Blood 108(13):4187–4193

    Article  PubMed  CAS  Google Scholar 

  155. Pepper C, Lowe H et al (2007) Fludarabine-mediated suppression of the excision repair enzyme ERCC1 contributes to the cytotoxic synergy with the DNA minor groove cross-linking agent SJG-136 (NSC 694501) in chronic lymphocytic leukaemia cells. Br J Cancer 97:253–259

    Article  PubMed  CAS  Google Scholar 

  156. Mukhopadhyay A, Elattar A et al (2010) Development of a functional assay for homologous recombination status in primary cultures of epithelial ovarian tumor and correlation with sensitivity to poly(ADP-ribose) polymerase inhibitors. Clin Cancer Res 16(8):2344–2351

    Article  PubMed  CAS  Google Scholar 

  157. Drew Y, Mulligan EA et al (2011) Therapeutic potential of poly(ADP-ribose) polymerase inhibitor AG014699 in human cancers with mutated or methylated BRCA1 or BRCA2. J Natl Cancer Inst 103(4):334–346

    Article  PubMed  CAS  Google Scholar 

  158. Friedmann B, Caplin M et al (2004) Modulation of DNA repair in vitro after treatment with chemotherapeutic agents by the epidermal growth factor receptor inhibitor gefitinib (ZD1839). Clin Cancer Res 10(19):6476–6486

    Article  PubMed  CAS  Google Scholar 

  159. Boone JJ, Bhosle J et al (2009) Involvement of the HER2 pathway in repair of DNA damage produced by chemotherapeutic agents. Mol Cancer Ther 8(11):3015–3023

    Article  PubMed  CAS  Google Scholar 

  160. Puzanov I, Lee W et al (2011) Phase I pharmacokinetic and pharmacodynamic study of SJG-136, a novel DNA sequence selective minor groove cross-linking agent, in advanced solid tumors. Clin Cancer Res 17(11):3794–3802

    Article  PubMed  CAS  Google Scholar 

  161. Middleton MR, Knox R et al (2010) Quinone oxidoreductase-2-mediated prodrug cancer therapy. Sci Transl Med 2(40):40ra50

    Article  PubMed  CAS  Google Scholar 

  162. Banuelos CA, Banath JP et al (2009) gammaH2AX expression in tumors exposed to cisplatin and fractionated irradiation. Clin Cancer Res 15(10):3344–3353

    Article  PubMed  CAS  Google Scholar 

  163. Clingen PH, Wu JY et al (2008) Histone H2AX phosphorylation as a molecular pharmacological marker for DNA interstrand crosslink cancer chemotherapy. Biochem Pharmacol 76(1):19–27

    Article  PubMed  CAS  Google Scholar 

  164. Hochhauser D, Meyer T et al (2009) Phase I study of sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors. Clin Cancer Res 15(6):2140–2147

    Article  PubMed  CAS  Google Scholar 

  165. Alley MC, Hollingshead MG et al (2004) SJG-136 (NSC 694501), a novel rationally designed DNA minor groove interstrand cross-linking agent with potent and broad spectrum antitumor activity: part 2: efficacy evaluations. Cancer Res 64(18):6700–6706

    Article  PubMed  CAS  Google Scholar 

  166. Hartley JA, Hamaguchi A et al (2010) SG2285, a novel C2-aryl-substituted pyrrolobenzodiazepine dimer prodrug that cross-links DNA and exerts highly potent antitumor activity. Cancer Res 70(17):6849–6858

    Article  PubMed  CAS  Google Scholar 

  167. Hartley JA, Hamaguchi A et al (2012) DNA interstrand cross-linking and in vivo antitumor activity of the extended pyrrolo[2,1-c][1,4]benzodiazepine dimer SG2057. Invest New Drugs 30(3):950–958

    Article  PubMed  CAS  Google Scholar 

  168. Both GW (2009) Recent progress in gene-directed enzyme prodrug therapy: an emerging cancer treatment. Curr Opin Mol Ther 11(4):421–432

    PubMed  CAS  Google Scholar 

  169. Mayer A, Francis RJ et al (2006) A phase I study of single administration of antibody-directed enzyme prodrug therapy with the recombinant anti-carcinoembryonic antigen antibody-enzyme fusion protein MFECP1 and a bis-iodo phenol mustard prodrug. Clin Cancer Res 12(21):6509–6516

    Article  PubMed  CAS  Google Scholar 

  170. Adair JR, Howard et al (2012) Antibody-drug conjugates - a perfect synergy. Expert Opin Biol Ther 12(9):1191–206

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK

    Anderson T. Wang & Peter J. McHugh

  2. UCL Cancer Institute, Faculty of Medical Sciences, University College London, London, UK

    John A. Hartley

Authors
  1. Anderson T. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter J. McHugh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John A. Hartley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John A. Hartley .

Editor information

Editors and Affiliations

  1. Jewish General Hospital, 3755 Cote Ste. Catherine Road, Montreal, H3T 1E2, Canada

    Lawrence Panasci

  2. , Department of Oncology, McGill University, 3755 CĂ´te Ste-Catherine Road, Montreal, H3T 1E2, Canada

    Raquel Aloyz

  3. McGill University, Department of Medicine and Oncology, Faculty of Medicine, 3755 CĂ´te Ste-Catherine Road, Montreal, H3T 1E2, Canada

    Moulay Alaoui-Jamali

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Wang, A.T., McHugh, P.J., Hartley, J.A. (2013). Repair of DNA Interstrand Cross-links Produced by Cancer Chemotherapeutic Drugs. In: Panasci, L., Aloyz, R., Alaoui-Jamali, M. (eds) Advances in DNA Repair in Cancer Therapy. Cancer Drug Discovery and Development, vol 72. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4741-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-4741-2_1

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-4740-5

  • Online ISBN: 978-1-4614-4741-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation