Recombination hot spot of hepatitis B virus genome binds to members of the HMG domain protein family and the Y box binding protein family; implication of these proteins in genomic instability.
OBJECTIVE
Previously we hypothesized that the occurrence of hepatocellular carcinoma (HCC) is enhanced by genomic instability induced by the integrated hepatitis B virus (HBV) DNA. Using an in vitro recombination assay, we showed that a subgenomic fragment of HBV DNA designated 15AB (nt1855-1914) is indispensable for in vitro recombination, and also showed the existence of 15AB binding protein. On the assumption that the 15AB binding protein may be a candidate cellular recombinogenic protein which accelerates genomic instability and hepatocarcinogenesis, we tried to isolate it by southwestern screening.


CONCLUSIONS
We obtained several positive clones including mouse upstream binding factor (UBF) and DNA binding protein A (dbpA). UBF belongs to an HMG domain protein family and dbpA belongs to a Y box binding protein family. 15AB binding seemed to be mediated by the conserved DNA binding domains in these families, because other members in the families such as HMG1 and YB-1 also bound to 15AB. We report them here because several documents have already suggested the possible association of these families and DNA recombination.
Kajino
K
K
Department of Experimental Pathology, Cancer Institute, Kami-Ikebukuro, Toshima-ku, Tokyo, Japan.
Yamamoto
T
T
Hayashi
J
J
Umeda
T
T
Takahara
T
T
Hino
O
O
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000821:virology; D002352:Carrier Proteins; D002908:Chronic Disease; D004249:DNA Damage / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016679:Genome, Viral; D024742:HMG-Box Domains; D024243:HMGB1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D008545:Melanoma / Q000235:genetics / Q000382:microbiology; D051379:Mice; D005810:Multigene Family; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016662:Virus Integration / Q000235:genetics; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; C408323:Csda protein, mouse; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; D006360:Heat-Shock Proteins; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D035463:Pol1 Transcription Initiation Complex Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C094867:YBX3 protein, human; C063844:transcription factor UBF