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. Author manuscript; available in PMC: 2014 Jul 15.
Published in final edited form as: Expert Opin Ther Targets. 2013 Aug 12;17(10):1119–1132. doi: 10.1517/14728222.2013.827663

Figure 2. HSV replication fork and model for model for coordinated leading- and lagging-strand DNA synthesis.

Figure 2

A. An HSV-1 replication fork would be expected to contain the helicase–primase complex (UL5/UL52/UL8) at the fork: UL5 would be expected to unwind duplex DNA ahead of the fork, and UL52 would be expected to lay down RNA primers that the two-subunit DNA polymerase (UL30/UL42) extends. The HSV-1 Pol also carries out leading-strand synthesis. ICP8 (UL29, SSB) presumably binds to ssDNA generated during HSV DNA synthesis. B. Coupled leading- and lagging-strand synthesis was recently reconstituted in vitro and requires HSV polymerase, helicase–primase and ICP8 [74]. In this model, coupled leading-and lagging-strand DNA synthesis requires two heterotrimers of helicase/primase and two molecules of the DNA polymerase. The leading- and lagging-strand polymerase molecules are proposed to communicate with each other through interactions between UL30 and the helicase–primase. A replication loop is formed in the lagging-strand to align it with the leading-strand. The lagging-strand DNA polymerase initiates Okazaki fragment synthesis using RNA primers (hatched bars).