Molecular cloning of a rat chromosome putative recombinogenic sequence homologous to the hepatitis B virus encapsidation signal.
Previously, we reported that a 61-bp subgenomic HBV DNA sequence (designated as 15AB, nt 1855-1915) is a hot spot for genomic recombination and that a cellular protein binding to 15AB may be the putative recombinogenic protein. In the present study, we established the existence of a 15AB-like sequence in human and rat chromosomal DNA by Southern blot analysis. The 15AB-like sequence isolated from the rat chromosome demonstrated a 80.9% identity with 5'-CCAAGCTGTGCCTTGGGTGGC-3', at 1872-1892 of the hepatitis B virus genome, thought to be the essential region for recombination. Interestingly, this 15AB-like sequence also contained the pentanucleotide motifs GCTGG and CCAGC as an inverted repeat, part of the chi known hot spot for recombination in Escherichia coli. Importantly, a portion of the 15AB-like sequence is homologous (82.1%, 23/28 bp) to break point clusters of the human promyelocytic leukemia (PML) gene, characterized by a translocation [t(15;17)], and to rearranged mouse DNA for the immunoglobulin kappa light chain. Moreover, 15AB and 15AB-like sequences have striking homologies (12/15 = 80.0% and 13/15 = 86.7%, respectively) to the consensus sequence for topoisomerase II. Our present results suggest that this 15AB-like sequence in the rat genome might be a recombinogenic candidate triggering genomic instability in carcinogenesis.
Aoki
H
H
Department of Experimental Pathology, Cancer Institue, Tokyo, Japan.
Kajino
K
K
Arakawa
Y
Y
Hino
O
O
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002213:Capsid / Q000235:genetics*; D002875:Chromosomes; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry; D017931:DNA Primers; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D000071156:Promyelocytic Leukemia Protein; D051381:Rats; D017208:Rats, Wistar / Q000235:genetics*; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D004247:DNA