DNA replication from two different worlds

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Science  22 Feb 2019:
Vol. 363, Issue 6429, pp. 814-815
DOI: 10.1126/science.aaw6265

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Replication of the DNA genome is performed by a replisome complex composed of numerous proteins. Cells have duplex DNA genomes, and their replisomes duplicate both strands simultaneously. A functional replisome requires, at a minimum, a helicase to unwind the DNA duplex, two DNA polymerases (Pols) to replicate the two DNA strands, and a primase to form RNA primers that DNA Pols extend. The replisome functions at a Y junction, or replication fork, and is a complex task because DNA Pols can only extend DNA in a 3′-to-5′ direction. Thus, as the helicase unwinds the antiparallel DNA strands, the DNA Pol on one strand (the leading strand) can go in the same direction as the helicase and replicate DNA continuously, but the DNA Pol on the antiparallel strand (the lagging strand) is generated in the opposite direction. This requires repeated priming and extension of the lagging strand discontinuously as a series of Okazaki fragments. This “semidiscontinuous replication” is shared by all cells. On page 835 of this issue, Gao et al. (1) report the cryo–electron microscopy (cryo-EM) structure of the T7 bacteriophage replisome at a high atomic detail. The study not only advances our understanding of the helicase mechanism but also reveals an unexpected arrangement of the two DNA Pols in the replisome. Specifically, the two Pols sandwich the DNA helicase in an asymmetric manner; one DNA Pol is on top of the helicase, and one DNA Pol is below (see the figure). This architecture is unlike textbook illustrations of both DNA Pols trailing behind the helicase.