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Hepatitis B virus impairs DNA damage responses by interfering with CUL4A-DDB1 ubiquitin ligase
2nd International Conference on Clinical Microbiology & Microbial Genomics
September 16-17, 2013 Hampton Inn Tropicana, Las Vegas, NV, USA

Cong Liu

Accepted Abstracts: J Microb Biochem Technol

Abstract:

Hepatocellular carcinoma (HCC) is one of the most deadly human cancers. Chronic hepatitis B virus (HBV) infection is known as the predominant risk factors associated with the development of HCC and complicates the treatment of HCC. It has been a long-term speculation that HBV disturb the cellular responses of DNA damage and the HBV-encoded oncogene (HBx) plays an important role in it, albeit the molecular mechanism behind it remains elusive. Here we report that cells harboring a HBV genome are defective in the early events of homologous recombination repair. Interestingly, ectopic expression of HBx recapitulates the phenotype of HBV infection in terms of ssDNA processing after DNA double strand breaks. Moreover, we found this impairment of DNA repair is associated with the ubiquitination activity of a SCF-like ubiquitin ligase, which is one of the key players of chromatin remodeling upon DNA damage. Thus, our work has provided compelling evidence that HBx is a potent cancer-promoting factor by debilitating DNA repair mechanism and possibly promotes accumulation of mutation in host cells.

Biography :

Cong Liu is now a professor of medicine in the West China Second University Hospital of Sichuan University. He got his B. Med in Public Health in West China University of Medical Sciences, continued Ph.D. study in biochemistry from University of Sussex, and got postdoctoral training in MRC/ Genome Damage and Stability Centre, UK. In 2009, he established the Laboratory of Genome Stability, part of the core research facility in Sichuan University, to study the mechanism of DNA repair and replication implicated in human diseases including cancer and oncogenic viral infection. His work has been supported by grants from Chinese National Science Foundation, Dept. of Education and Dept. of Science and Technology of central government. He was also awarded by local and central government as distinguished young scientist. He has published more than 13 peer-reviewed papers in reputed academic journals.