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The hepatitis B virus x protein inhibits thymine DNA glycosylase initiated base excision repair.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (11), pp. e48940. Date of Electronic Publication: 2012 Nov 08. - Publication Year :
- 2012
-
Abstract
- The hepatitis B virus (HBV) genome encodes the X protein (HBx), a ubiquitous transactivator that is required for HBV replication. Expression of the HBx protein has been associated with the development of HBV infection-related hepatocellular carcinoma (HCC). Previously, we generated a 3D structure of HBx by combined homology and ab initio in silico modelling. This structure showed a striking similarity to the human thymine DNA glycosylase (TDG), a key enzyme in the base excision repair (BER) pathway. To further explore this finding, we investigated whether both proteins interfere with or complement each other's functions. Here we show that TDG does not affect HBV replication, but that HBx strongly inhibits TDG-initiated base excision repair (BER), a major DNA repair pathway. Inhibition of the BER pathway may contribute substantially to the oncogenic effect of HBV infection.
- Subjects :
- Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular virology
DNA Replication
HEK293 Cells
Hep G2 Cells
Hepatitis B genetics
Hepatitis B metabolism
Hepatitis B virology
Humans
Liver Neoplasms genetics
Liver Neoplasms metabolism
Liver Neoplasms virology
Thymine DNA Glycosylase genetics
Thymine DNA Glycosylase metabolism
Viral Regulatory and Accessory Proteins
DNA Repair
Thymine DNA Glycosylase antagonists & inhibitors
Trans-Activators genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23145031
- Full Text :
- https://doi.org/10.1371/journal.pone.0048940