title: Lytic infection of Kaposi's sarcoma-associated herpesvirus induces DNA double-strand breaks and impairs non-homologous end joining.
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.
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Jungang
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Qingjiao
authors.initials: Q
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Can
authors.initials: C
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Xulin
authors.initials: X
authors.lastname: Chen
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism*; D053960:DNA Breaks; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D000072200:Ku Autoantigen; D011485:Protein Binding; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C110348:ORF59 protein, Human herpesvirus 8; D014764:Viral Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen