DNA Interstrand Crosslink Repair and Cancer

Overview

Journal Nat Rev Cancer

Specialty Oncology

Date 2011 Jun 25

PMID 21701511

Citations 533

Authors

Andrew J Deans

Stephen C West

Affiliations

Soon will be listed here.

Abstract

Interstrand crosslinks (ICLs) are highly toxic DNA lesions that prevent transcription and replication by inhibiting DNA strand separation. Agents that induce ICLs were one of the earliest, and are still the most widely used, forms of chemotherapeutic drug. Only recently, however, have we begun to understand how cells repair these lesions. Important insights have come from studies of individuals with Fanconi anaemia (FA), a rare genetic disorder that leads to ICL sensitivity. Understanding how the FA pathway links nucleases, helicases and other DNA-processing enzymes should lead to more targeted uses of ICL-inducing agents in cancer treatment and could provide novel insights into drug resistance.

Citing Articles

Epithelial competition determines gene therapy potential to suppress Fanconi Anemia oral cancer risk.

Colegrove H, Monnat R, Monnat Jr R, Feder A bioRxiv. 2025; .

PMID: 40060430 PMC: 11888451. DOI: 10.1101/2025.02.26.640284.

Long-term pulmonary complications in sulfur mustard-exposed patients: gene expression and DNA methylation of OGG1.

Zamani M, Ghazanfari T Bioimpacts. 2025; 15:27735.

PMID: 39963564 PMC: 11830137. DOI: 10.34172/bi.2023.27735.

Genetic Analysis of Intraductal Carcinoma of the Prostate Detected in High-Grade Prostatic Intraepithelial Neoplasia Cases.

Watanabe R, Miura N, Kurata M, Kitazawa R, Kikugawa T, Saika T Cureus. 2025; 16(12):e76165.

PMID: 39840193 PMC: 11747056. DOI: 10.7759/cureus.76165.

Evaluation of BRIP-1 (FANCJ) and FANCI Protein Expression in Ovarian Cancer Tissue.

Kozlowski M, Borzyszkowska D, Golara A, Durys D, Piotrowska K, Kempinska-Podhorodecka A Biomedicines. 2025; 12(12.

PMID: 39767562 PMC: 11673538. DOI: 10.3390/biomedicines12122652.

Molecular dependencies and genomic consequences of a global DNA damage tolerance defect.

de Groot D, Spanjaard A, Shah R, Kreft M, Morris B, Lieftink C Genome Biol. 2024; 25(1):323.

PMID: 39741332 PMC: 11687044. DOI: 10.1186/s13059-024-03451-z.

References

Hirsch B, Shimamura A, Moreau L, Baldinger S, Hag-alshiekh M, Bostrom B . Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood. Blood. 2003; 103(7):2554-9. DOI: 10.1182/blood-2003-06-1970. View

Chaganti R, Schonberg S, German J . A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes. Proc Natl Acad Sci U S A. 1974; 71(11):4508-12. PMC: 433916. DOI: 10.1073/pnas.71.11.4508. View

Howlett N, Harney J, Rego M, Kolling 4th F, Glover T . Functional interaction between the Fanconi Anemia D2 protein and proliferating cell nuclear antigen (PCNA) via a conserved putative PCNA interaction motif. J Biol Chem. 2009; 284(42):28935-42. PMC: 2781439. DOI: 10.1074/jbc.M109.016352. View

Moldovan G, Madhavan M, Mirchandani K, McCaffrey R, Vinciguerra P, DAndrea A . DNA polymerase POLN participates in cross-link repair and homologous recombination. Mol Cell Biol. 2009; 30(4):1088-96. PMC: 2815579. DOI: 10.1128/MCB.01124-09. View

Dunnick J, Forbes P, Davies R, Iverson W . Toxicity of 8-methoxypsoralen, 5-methoxypsoralen, 3-carbethoxypsoralen, or 5-methylisopsoralen with ultraviolet radiation in the hairless (HRA/Skh) mouse. Toxicol Appl Pharmacol. 1987; 89(1):73-80. DOI: 10.1016/0041-008x(87)90177-3. View

Kratz K, Schopf B, Kaden S, Sendoel A, Eberhard R, Lademann C . Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell. 2010; 142(1):77-88. DOI: 10.1016/j.cell.2010.06.022. View

Wang H, Zeng Z, Bui T, Dibiase S, Qin W, Xia F . Nonhomologous end-joining of ionizing radiation-induced DNA double-stranded breaks in human tumor cells deficient in BRCA1 or BRCA2. Cancer Res. 2001; 61(1):270-7. View

Vasey P, Jayson G, Gordon A, Gabra H, Coleman R, Atkinson R . Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004; 96(22):1682-91. DOI: 10.1093/jnci/djh323. View

Rai K, Peterson B, Appelbaum F, Kolitz J, Elias L, Shepherd L . Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000; 343(24):1750-7. DOI: 10.1056/NEJM200012143432402. View

10.

Pegram M, Pienkowski T, Northfelt D, Eiermann W, Patel R, Fumoleau P . Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. J Natl Cancer Inst. 2004; 96(10):759-69. DOI: 10.1093/jnci/djh133. View

11.

Woodward A, Gohler T, Luciani M, Oehlmann M, Ge X, Gartner A . Excess Mcm2-7 license dormant origins of replication that can be used under conditions of replicative stress. J Cell Biol. 2006; 173(5):673-83. PMC: 2063885. DOI: 10.1083/jcb.200602108. View

12.

Hussain S, Stocken D, Peake D, Glaholm J, Zarkar A, Wallace D . Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer. Br J Cancer. 2004; 90(11):2106-11. PMC: 2409507. DOI: 10.1038/sj.bjc.6601852. View

13.

Meetei A, Medhurst A, Ling C, Xue Y, Singh T, Bier P . A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005; 37(9):958-63. PMC: 2704909. DOI: 10.1038/ng1626. View

14.

Yan Z, Delannoy M, Ling C, Daee D, Osman F, Muniandy P . A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol Cell. 2010; 37(6):865-78. PMC: 2847587. DOI: 10.1016/j.molcel.2010.01.039. View

15.

Thorslund T, McIlwraith M, Compton S, Lekomtsev S, Petronczki M, Griffith J . The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA. Nat Struct Mol Biol. 2010; 17(10):1263-5. PMC: 4041013. DOI: 10.1038/nsmb.1905. View

16.

Ahn J, Ko W, Lee J, Shim K, Jeung H, Park J . Effect of vinorelbine, ifosfamide, and cisplatin combination chemotherapy in advanced non-small-cell lung cancer. Am J Clin Oncol. 2001; 23(6):622-8. DOI: 10.1097/00000421-200012000-00020. View

17.

Quentin S, Cuccuini W, Ceccaldi R, Nibourel O, Pondarre C, Pages M . Myelodysplasia and leukemia of Fanconi anemia are associated with a specific pattern of genomic abnormalities that includes cryptic RUNX1/AML1 lesions. Blood. 2011; 117(15):e161-70. DOI: 10.1182/blood-2010-09-308726. View

18.

Roques C, Coulombe Y, Delannoy M, Vignard J, Grossi S, Brodeur I . MRE11-RAD50-NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair. EMBO J. 2009; 28(16):2400-13. PMC: 2735166. DOI: 10.1038/emboj.2009.193. View

19.

Janjigian Y, Lee W, Kris M, Miller V, Krug L, Azzoli C . A phase I trial of SJG-136 (NSC#694501) in advanced solid tumors. Cancer Chemother Pharmacol. 2009; 65(5):833-8. PMC: 3711187. DOI: 10.1007/s00280-009-1088-4. View

20.

Vaz F, Hanenberg H, Schuster B, Barker K, Wiek C, Erven V . Mutation of the RAD51C gene in a Fanconi anemia-like disorder. Nat Genet. 2010; 42(5):406-9. DOI: 10.1038/ng.570. View