THE MODE OF HEPATITIS-B VIRUS-DNA INTEGRATION IN CHROMOSOMES OF HUMAN HEPATOCELLULAR-CARCINOMA

THE MODE OF HEPATITIS-B VIRUS-DNA INTEGRATION IN CHROMOSOMES OF HUMAN HEPATOCELLULAR-CARCINOMA
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DOI:
10.1101/gad.1.8.773
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发表时间:
1987-10-01
影响因子:
10.5
通讯作者:
MATSUBARA, K
MATSUBARA, K
中科院分区:
生物学1区
文献类型:
--
作者:
NAGAYA, T;NAKAMURA, T;MATSUBARA, K

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用分子克隆技术从7例肝癌组织中分离出19例携带整合型B型肝炎病毒(HBV)DNA的DNA,并测定了它们的结构。结果,结合报告的数据,进行了分析,以便人们可以获得深入了解这种病毒DNA的整合机制和随后发生的可能重排。DNA连接点沿着病毒基因组的分布表明存在重组熟练区域。因此,大约一半的整合子是Coh型,即,其中一个病毒-细胞DNA连接点位于病毒基因组中两个11-bp同向重复序列(DR 1和DR 2)之间的所谓粘性末端区域内,基因组的转录和复制在该区域启动。所有整合的病毒基因组至少在粘性末端区域周围的一个位点有缺陷,特别是在X基因内。重组熟练区域不仅用于病毒-细胞的形成,还用于病毒-病毒连接的形成。无论是病毒还是细胞DNA在连接处都没有显示出独特的序列,整合的靶点位于许多不同的染色体上。
Nineteen DNA samples that carry integrated hepatitis B virus (HBV) DNA were isolated from seven independent human hepatomas by molecular cloning, and their structures were determined. The results, combined with reported data, were analyzed so that one can obtain insights into the mechanisms of integration of this virus DNA and possible rearrangements that occur subsequently. The distribution of DNA junctions along the virus genome suggests that there are recombination-proficient regions. Thus, about half of the integrants were the Coh type, viz., one of their virus-cell DNA junctions fell within the so-called cohesive end region that lies between two 11-bp direct repeats (DR1 and DR2) in the virus genome where transcription and replication of the genome are initiated. All the integrated virus genomes were defective at least in one site around the cohesive end region, particularly within the X gene. The recombination-proficient regions are used not only for formation of virus-cell but also of virus-virus junctions. Neither virus nor cell DNA show unique sequences at the junctions, and targets for integration lie on many different chromosomes.