1887

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) has been associated with the development of Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease. Cytogenetic studies have revealed chromosome abnormalities in KS tissues, including recurring copy number changes in chromosomes and the loss of chromosomes. Unfaithful DNA repair may contribute to the genomic instability that is one of the most common hallmarks of tumours. We found that lytic infection of KSHV can cause severe DNA double-strand breaks (DSBs) and impair non-homologous end joining (NHEJ) in host cells. Processivity factor 8 (PF-8) of KSHV was identified as interacting with Ku70 and Ku86, and the interaction was dependent on DSBs and DNA. Overexpression of PF-8 in HeLa cells impaired NHEJ by blocking the interaction between the Ku complex and the DNA-dependent protein kinase catalytic subunit. These results suggest that KSHV lytic replication may contribute to tumorigenesis by causing DNA DSBs and interfering with the repair of DSBs.

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2013-08-01
2019-10-16
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References

  1. Ablashi D. V., Chatlynne L. G., Whitman J. E. Jr, Cesarman E.. ( 2002; ). Spectrum of Kaposi’s sarcoma-associated herpesvirus, or human herpesvirus 8, diseases. . Clin Microbiol Rev 15:, 439–464. [CrossRef] [PubMed]
    [Google Scholar]
  2. An J., Sun Y., Fisher M., Rettig M. B.. ( 2004; ). Antitumor effects of bortezomib (PS-341) on primary effusion lymphomas. . Leukemia 18:, 1699–1704. [CrossRef] [PubMed]
    [Google Scholar]
  3. Burma S., Chen B. P., Chen D. J.. ( 2006; ). Role of non-homologous end joining (NHEJ) in maintaining genomic integrity. . DNA Repair (Amst) 5:, 1042–1048. [CrossRef] [PubMed]
    [Google Scholar]
  4. Casper C.. ( 2005; ). The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care. . Br J Haematol 129:, 3–17. [CrossRef] [PubMed]
    [Google Scholar]
  5. Chen X., Lin K., Ricciardi R. P.. ( 2004; ). Human Kaposi’s sarcoma herpesvirus processivity factor-8 functions as a dimer in DNA synthesis. . J Biol Chem 279:, 28375–28386. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chronowski G. M., Ha C. S., Wilder R. B., Cabanillas F., Manning J., Cox J. D.. ( 2001; ). Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy. . Cancer 92:, 670–676. [CrossRef] [PubMed]
    [Google Scholar]
  7. Deriano L., Guipaud O., Merle-Béral H., Binet J. L., Ricoul M., Potocki-Veronese G., Favaudon V., Maciorowski Z., Muller C.. & other authors ( 2005; ). Human chronic lymphocytic leukemia B cells can escape DNA damage-induced apoptosis through the nonhomologous end-joining DNA repair pathway. . Blood 105:, 4776–4783. [CrossRef] [PubMed]
    [Google Scholar]
  8. Fowler R. A., Meyskens F. L. Jr. ( 1978; ). Tumor viruses and human cancer. II. DNA tumor viruses. . Ariz Med 35:, 661–662, 666–667.[PubMed]
    [Google Scholar]
  9. Gaspar M., Shenk T.. ( 2006; ). Human cytomegalovirus inhibits a DNA damage response by mislocalizing checkpoint proteins. . Proc Natl Acad Sci U S A 103:, 2821–2826. [CrossRef] [PubMed]
    [Google Scholar]
  10. Gholam D., Vantelon J. M., Al-Jijakli A., Bourhis J. H.. ( 2003; ). A case of multicentric Castleman’s disease associated with advanced systemic amyloidosis treated with chemotherapy and anti-CD20 monoclonal antibody. . Ann Hematol 82:, 766–768. [CrossRef] [PubMed]
    [Google Scholar]
  11. Green M., Wold W. S.. ( 1976; ). Oncogenic DNA viruses–replication, tumor gene expression, and role in human cancer. . Semin Oncol 3:, 65–79.[PubMed]
    [Google Scholar]
  12. Hayward G. S.. ( 2003; ). Initiation of angiogenic Kaposi’s sarcoma lesions. . Cancer Cell 3:, 1–3. [CrossRef] [PubMed]
    [Google Scholar]
  13. Herrada J., Cabanillas F., Rice L., Manning J., Pugh W.. ( 1998; ). The clinical behavior of localized and multicentric Castleman disease. . Ann Intern Med 128:, 657–662. [CrossRef] [PubMed]
    [Google Scholar]
  14. Jenner R. G., Albà M. M., Boshoff C., Kellam P.. ( 2001; ). Kaposi’s sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. . J Virol 75:, 891–902. [CrossRef] [PubMed]
    [Google Scholar]
  15. Jha H. C., Upadhyay S. K., Aj M. P., Lu J., Cai Q., Saha A., Robertson E. S.. ( 2013; ). H2AX phosphorylation is important for LANA-mediated Kaposi’s sarcoma-associated herpesvirus episome persistence. . J Virol 87:, 5255–5269. [CrossRef] [PubMed]
    [Google Scholar]
  16. Kao J., Rosenstein B. S., Peters S., Milano M. T., Kron S. J.. ( 2005; ). Cellular response to DNA damage. . Ann N Y Acad Sci 1066:, 243–258. [CrossRef] [PubMed]
    [Google Scholar]
  17. Kudoh A., Fujita M., Zhang L., Shirata N., Daikoku T., Sugaya Y., Isomura H., Nishiyama Y., Tsurumi T.. ( 2005; ). Epstein–Barr virus lytic replication elicits ATM checkpoint signal transduction while providing an S-phase-like cellular environment. . J Biol Chem 280:, 8156–8163. [CrossRef] [PubMed]
    [Google Scholar]
  18. Kumari P., Schechter G. P., Saini N., Benator D. A.. ( 2000; ). Successful treatment of human immunodeficiency virus-related Castleman’s disease with interferon-alpha. . Clin Infect Dis 31:, 602–604. [CrossRef] [PubMed]
    [Google Scholar]
  19. Lord C. J., Ashworth A.. ( 2012; ). The DNA damage response and cancer therapy. . Nature 481:, 287–294. [CrossRef] [PubMed]
    [Google Scholar]
  20. Mladenov E., Kalev P., Anachkova B.. ( 2009; ). The complexity of double-strand break ends is a factor in the repair pathway choice. . Radiat Res 171:, 397–404. [CrossRef] [PubMed]
    [Google Scholar]
  21. Nair P., Pan H., Stallings R. L., Gao S. J.. ( 2006; ). Recurrent genomic imbalances in primary effusion lymphomas. . Cancer Genet Cytogenet 171:, 119–121. [CrossRef] [PubMed]
    [Google Scholar]
  22. Nishimoto N., Kanakura Y., Aozasa K., Johkoh T., Nakamura M., Nakano S., Nakano N., Ikeda Y., Sasaki T.. & other authors ( 2005; ). Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease. . Blood 106:, 2627–2632. [CrossRef] [PubMed]
    [Google Scholar]
  23. Pan H., Zhou F., Gao S. J.. ( 2004; ). Kaposi’s sarcoma-associated herpesvirus induction of chromosome instability in primary human endothelial cells. . Cancer Res 64:, 4064–4068. [CrossRef] [PubMed]
    [Google Scholar]
  24. Pastwa E., Błasiak J.. ( 2003; ). Non-homologous DNA end joining. . Acta Biochim Pol 50:, 891–908.[PubMed]
    [Google Scholar]
  25. Pastwa E., Neumann R. D., Mezhevaya K., Winters T. A.. ( 2003; ). Repair of radiation-induced DNA double-strand breaks is dependent upon radiation quality and the structural complexity of double-strand breaks. . Radiat Res 159:, 251–261. [CrossRef] [PubMed]
    [Google Scholar]
  26. Popescu N. C., Zimonjic D. B., Leventon-Kriss S., Bryant J. L., Lunardi-Iskandar Y., Gallo R. C.. ( 1996; ). Deletion and translocation involving chromosome 3 (p14) in two tumorigenic Kaposi’s sarcoma cell lines. . J Natl Cancer Inst 88:, 450–455. [CrossRef] [PubMed]
    [Google Scholar]
  27. Pyakurel P., Montag U., Castaños-Vélez E., Kaaya E., Christensson B., Tönnies H., Biberfeld P., Heiden T.. ( 2006; ). CGH of microdissected Kaposi’s sarcoma lesions reveals recurrent loss of chromosome Y in early and additional chromosomal changes in late tumour stages. . AIDS 20:, 1805–1812. [CrossRef] [PubMed]
    [Google Scholar]
  28. Rogakou E. P., Pilch D. R., Orr A. H., Ivanova V. S., Bonner W. M.. ( 1998; ). DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. . J Biol Chem 273:, 5858–5868. [CrossRef] [PubMed]
    [Google Scholar]
  29. Seluanov A., Mittelman D., Pereira-Smith O. M., Wilson J. H., Gorbunova V.. ( 2004; ). DNA end joining becomes less efficient and more error-prone during cellular senescence. . Proc Natl Acad Sci U S A 101:, 7624–7629. [CrossRef] [PubMed]
    [Google Scholar]
  30. Shirata N., Kudoh A., Daikoku T., Tatsumi Y., Fujita M., Kiyono T., Sugaya Y., Isomura H., Ishizaki K., Tsurumi T.. ( 2005; ). Activation of ataxia telangiectasia-mutated DNA damage checkpoint signal transduction elicited by herpes simplex virus infection. . J Biol Chem 280:, 30336–30341. [CrossRef] [PubMed]
    [Google Scholar]
  31. Thompson S. L., Compton D. A.. ( 2011; ). Chromosomes and cancer cells. . Chromosome Res 19:, 433–444. [CrossRef] [PubMed]
    [Google Scholar]
  32. Valladares Y.. ( 1967; ). Cancerigenic viruses neoformed in in vitro cultured cells starting on DNA from human cancer cells. . Med Pharmacol Exp Int J Exp Med 16:, 311–324.[PubMed]
    [Google Scholar]
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