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 (desi gnated as 15AB, nt 1855-1915) is a hot spot for genomic: recombination and that a cellular protein binding to 15AB may be the putative recom binogenic protein, In the present study, we established the existense of a 15AB-like sequence in human and rat chromosomal DNA by Southern b lot analysis, The 15AB-like sequence isolated from the rat chromosome demonstrated a 80.9% identity with 5'-CCAAGCTGTGCCTTGGGTGGC-3', nt 187 2-1892 of the hepatitis B virus genome, thought to be the essential re gion for recombination, Interestingly, this 15AB-like sequence also co ntained the pentanucleotide motifs GCTGG and CCAGC as an inverted repe at, part of the chi known hot spot for recombination in Escherichia co li, Importantly, a portion of the 15AB-like sequence is homologous (82 .1%, 23/28 bp) to break point clusters of the human promyelocytic leuk emia (PML) gene, characterized by a translocation [t(15;17)], and to r earranged 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 topois omerase II, Our present results suggest that this 15AB-like sequence i n the rat genome might be a recombinogenic candidate triggering genomi c instability in carcinogenesis.