Aoki H, Kajino K, Arakawa Y, Hino O
Department of Experimental Pathology, Cancer Institue, Tokyo, Japan.
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7300-4. doi: 10.1073/pnas.93.14.7300.
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.
此前，我们报道了一个61个碱基对的亚基因组乙肝病毒DNA序列（命名为15AB，核苷酸1855 - 1915）是基因组重组的热点，并且与15AB结合的一种细胞蛋白可能是假定的重组蛋白。在本研究中，我们通过Southern印迹分析证实了在人和大鼠染色体DNA中存在15AB样序列。从大鼠染色体分离出的15AB样序列与乙肝病毒基因组1872 - 1892处的5'-CCAAGCTGTGCCTTGGGTGGC-3'显示出80.9%的同一性，该区域被认为是重组的关键区域。有趣的是，这个15AB样序列还包含五核苷酸基序GCTGG和CCAGC作为反向重复，这是大肠杆菌中已知的重组热点chi的一部分。重要的是，15AB样序列的一部分与人类早幼粒细胞白血病（PML）基因的断裂点簇同源（82.1%，23/28碱基对），该基因的特征是易位[t(15;17)]，并且与免疫球蛋白κ轻链的重排小鼠DNA同源。此外，15AB和15AB样序列与拓扑异构酶II的共有序列具有显著的同源性（分别为12/15 = 80.0%和13/15 = 86.7%）。我们目前的结果表明，大鼠基因组中的这个15AB样序列可能是一个重组候选物，在致癌过程中引发基因组不稳定。
