Nature：DNA复制控制新发现

　　

生物通报道，哈佛大学医学院生物化学与分子制药系的科学家Antonie M.van Oijen和Charles C.Richardson带领的研究小组在DNA复制方面的研究取得新进展，相关成果公布在11月23日的Nature上。

 

研究小组认为，DNA复制环的动力学体现了DNA复制过程中延迟链复制的暂时性调控机制。

 

在所有的生物体中，DNA复制的定向性问题都受蛋白调控的机制影响。逆向的天然双链DNA允许先合成链聚合酶延续DNA的复制，然后形成延后链聚合酶促进反向链（互补链）的合成。通过延伸引物RNA延后链聚合酶在间隔一个短的时间后，重新启动合成冈崎片段。

在原核系统中，为解决方向性的问题，延后链在复制叉后形成一个复制环，适应延后链聚合酶的复制过程，这一过程可促进延后链更好地与先合成链的衔接。在冈崎片段形成的循环过程中，复制环逐渐变大然后再皱缩以适应该过程。

 

在本研究中，科学家们用单分子技术实时观察噬菌体T7DNA复制过程中的复制环的变化情况。分析复制环形成的大小，滞后时间，这些都表明引物合成的启动和冈崎片段的合成完成都是促进复制环释放的因素。这两个因素共同维持复制环的启动是DNA复制系统的一个保障机制，确保每合成一个冈崎片段后复制行为可持续进行直到复制过程完成。

 

原文摘要：Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

 

【Abstract】

In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to synthesize in the opposite direction. By extending RNA primers, the lagging-strand polymerase restarts at short intervals and produces Okazaki fragments1, 2. At least in prokaryotic systems, this directionality problem is solved by the formation of a loop in the lagging strand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in parallel with the leading-strand polymerase. The replication loop grows and shrinks during each cycle of Okazaki fragment synthesis3. Here we use single-molecule techniques to visualize, in real time, the formation and release of replication loops by individual replisomes of bacteriophage T7 supporting coordinated DNA replication. Analysis of the distributions of loop sizes and lag times between loops reveals that initiation of primer synthesis and the completion of an Okazaki fragment each serve as a trigger for loop release. The presence of two triggers may represent a fail-safe mechanism ensuring the timely reset of the replisome after the synthesis of every Okazaki fragment.

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