Hamlin J L
University of Virginia School of Medicine, Charlottesville 22908.
Bioessays. 1992 Oct;14(10):651-9. doi: 10.1002/bies.950141002.
It has been almost twenty-five years since Huberman and Riggs first showed that there are multiple bidirectional origins of replication scattered at approximately 100 kb intervals along mammalian chromosomal fibers. Since that time, every conceivable physical property unique to replicating DNA has been taken advantage of to determine whether origins of replication are defined sequence elements, as they are in microorganisms. The most thoroughly studied mammalian locus to date is the dihydrofolate reductase domain of Chinese hamster cells, which will be used as a model to discuss the various methods of investigation. While several laboratories agree on the rough location of the 'initiation locus' in this large chromosomal domain, different experimental approaches paint different pictures of the mechanism by which initiation occurs. However, a variety of new techniques and synchronizing agents promises to clarify the picture for this particular locus, and to provide the means for identifying and isolating other origins of replication for comparison.
自休伯曼和里格斯首次表明沿着哺乳动物染色体纤维以大约100千碱基的间隔散布着多个双向复制起点以来，已经过去了近25年。从那时起，人们利用了复制DNA特有的每一种可以想象到的物理特性，来确定复制起点是否像在微生物中那样是特定的序列元件。迄今为止研究最深入的哺乳动物基因座是中国仓鼠细胞的二氢叶酸还原酶结构域，它将作为一个模型来讨论各种研究方法。虽然几个实验室对这个大染色体结构域中“起始基因座”的大致位置达成了一致，但不同的实验方法描绘了不同的起始发生机制。然而，各种新技术和同步剂有望澄清这个特定基因座的情况，并提供识别和分离其他复制起点以便进行比较的方法。
