Mammalian DNA polymerases alpha and delta: current status in DNA replication.

Mammalian DNA polymerases alpha and delta: current status in DNA replication.
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哺乳动物 DNA 聚合酶 α 和 δ:DNA 复制的现状。

DOI:
10.1021/bi00413a001
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发表时间:
1988
期刊:
影响因子:
2.9
通讯作者:
Downey,KM
Downey,KM
中科院分区:
生物学3区
文献类型:
--
作者:
So,AG;Downey,KM

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早期试图在DNA聚合酶水平上理解染色体DNA的复制,这些DNA聚合酶催化核苷酸的模板定向聚合,但由于需要适应复制叉的单向运动和所有DNA聚合酶合成的专性5‘到3’方向,因此失败了。当发现只有一条新的DNA链,即前导链,在与生长点整体运动方向一致的5‘到3’方向上连续合成,而另一条链,即滞后链,在与叉整体运动方向相反的5‘到3’方向上不连续合成时,这个难题就解决了。研究发现,滞后链的不连续合成涉及RNA引物、引物去除、间隙填充以及最终通过连接酶将滞后链片段(Okazaki片段)连接(Kornberg, 1980, 1982)。前导链和滞后链合成的阐明,使叉运动的单向性与核苷酸聚合的专性5′~ 3′方向相协调;然而,它提出了一个新问题。虽然单个DNA聚合酶被认为在原核生物中催化前导链和滞后链的合成,但催化前导链合成的复制酶的功能特性预计将与滞后链复制酶的功能特性大不相同。例如,前导链复制酶应该具有高度的进程性,一旦与replicón结合,在完全复制之前保持关联,而后链复制酶对模板的亲和力应该明显较低,因为它必须能够在合成每个冈崎片段后与DNA分离。这些考虑导致了原核生物复制叉模型的产生,其中前导链和后导链的合成都是由一个复制复合体进行的。这项工作得到了NIH拨款DK26206和NSF拨款8703747的部分支持。
Efarly attempts to understand the replication of chromosomal DNA at the level of the DNA polymerases that catalyze the template-directed polymerization of nucleotides were con-founded by the need to accommodate both the unidirectional movement of the replication fork and the obligate 5'to 3'direction of synthesis of all DNA polymerases. This con-undrum was resolved when it was found that only one of the new DNA strands, the leading strand, was synthesized con-tinuously in the 5'to 3'direction coinciding with the overall movement of the growing point, and the other strand, the lagging strand, was synthesized discontinuously in the 5'to 3'direction opposite to the overall direction of movement of the fork. Discontinuous synthesis of the lagging strand was found to involve RNA priming, primerremoval, gap filling, and the eventual joining of the lagging strand segments (Okazaki fragments) by a ligase (Kornberg, 1980, 1982). The elucidation of leading strand and lagging strand synthesis reconciled theunidirectional nature of fork movement with the obligate 5'to 3'direction of nucleotide polymerization; however, it raised a new problem. Although a single DNA polymerase is thought to catalyze both leading strand and lagging strand synthesis in prokaryotes, the functional prop-erties of a replicase that catalyzes leading strand synthesis would be expected to be quite different from those required of a lagging strand replicase. For example, a leading strand replicase should be highly processive and, once bound to a replicón, remain associated until it is completely replicated, whereas a lagging strand replicase shouldhave a significantly lower affinity for the template as it must be able to dissociate from the DNA after synthesizing each Okazaki fragment. These considerations have given rise to replication fork models in prokaryotes in which synthesis of both the leading and lagging strands is carried out by a replication complex that f This work was supported in part by NIH Grant DK26206 and NSF Grant 8703747.
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