Article

Replication and Recombination of Herpes Simplex Virus DNA

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Journal of Biological Chemistry (Impact Factor: 4.57). 03/2011; 286(18):15619-24. DOI: 10.1074/jbc.R111.233981
Source: PubMed

ABSTRACT Replication of herpes simplex virus takes place in the cell nucleus and is carried out by a replisome composed of six viral proteins: the UL30-UL42 DNA polymerase, the UL5-UL8-UL52 helicase-primase, and the UL29 single-stranded DNA-binding protein ICP8. The replisome is loaded on origins of replication by the UL9 initiator origin-binding protein. Virus replication is intimately coupled to recombination and repair, often performed by cellular proteins. Here, we review new significant developments: the three-dimensional structures for the DNA polymerase, the polymerase accessory factor, and the single-stranded DNA-binding protein; the reconstitution of a functional replisome in vitro; the elucidation of the mechanism for activation of origins of DNA replication; the identification of cellular proteins actively involved in or responding to viral DNA replication; and the elucidation of requirements for formation of replication foci in the nucleus and effects on protein localization.

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    • "ICP8 also binds to RNA albeit with reduced affinity compared to its ssDNA binding activity [19]. Functionally, ICP8 performs a critical role at the viral DNA replication fork by maintaining ssDNA regions and by interacting with various other replisome components via specific protein–protein interactions [reviewed in [20] [21] [22] [23] [24]]. In addition, ICP8 has been demonstrated to function as a recombinase, capable of promoting strand annealing and strand invasion as well as mediating strand exchange reactions in conjunction with the HSV-1 helicase-primase or UL12 nuclease [25] [26] [27] [28]. "
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