c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene
c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene
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DOI：
10.1038/sj.onc.1205145
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发表时间：
2002-01-31
期刊：
影响因子：
8
通讯作者：
Mai, S
中科院分区：
文献类型：
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作者：
Kuschak, TI;Kuschak, BC;Mai, S
癌蛋白c-Myc启动位点特异性基因扩增的机制尚不清楚。在分析小鼠核糖核苷酸还原酶R2 （R2）基因c- myc依赖性扩增的启动机制时，我们观察到c- myc依赖性启动R2基因的非法DNA复制。我们证明了多个同时发生的c- myc诱导的R2复制分叉，而R2通常用单个分叉进行复制。相反，无论C - myc解除调控与否，周期蛋白C仅用一个复制叉进行复制。除了从头开始复制叉外，c-Myc还启动R2的双等位基因复制，取消其正常的单等位基因复制模式。此外，一些染色体区域也显示c-Myc诱导的非法复制谱。因此，c-Myc可以作为一种非法复制许可因子，促进从头复制起始和非法复制时间，对基因组稳定性产生不利影响。
The mechanisms through which the oncoprotein c-Myc initiates locus-specific gene amplification are not understood. When analysing the initiation mechanism of c-Myc-dependent amplification of the mouse ribonucleotide reductase R2 (R2) gene, we observe c-Myc-dependent initiation of illegitimate DNA replication of the R2 gene. We demonstrate multiple simultaneous c-Myc-induced R2 replication forks, whereas R2 normally replicates with a single fork. In contrast, cyclin C replicates with only a single replication fork irrespective of c-Myc deregulation. In addition to de novo replication forks, c-Myc also initiates bi-allelic replication of R2, abrogating its normal mono-allelic replication pattern, Moreover, several chromosomal regions also display c-Myc-induced illegitimate replication profiles. Thus, c-Myc can act as an illegitimate replication-licensing factor that promotes de novo replication initiation and illegitimate replication timing that adversely impacts upon genomic stability.