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Review
. 2009 Feb 20;384(2):352-9.
doi: 10.1016/j.virol.2008.11.038. Epub 2008 Dec 20.

SV40 DNA replication: from the A gene to a nanomachine

Ellen Fanning  1 , Kun Zhao
Affiliations
Review

SV40 DNA replication: from the A gene to a nanomachine

Ellen Fanning et al. Virology. .

Abstract

Duplication of the simian virus 40 (SV40) genome is the best understood eukaryotic DNA replication process to date. Like most prokaryotic genomes, the SV40 genome is a circular duplex DNA organized in a single replicon. This small viral genome, its association with host histones in nucleosomes, and its dependence on the host cell milieu for replication factors and precursors led to its adoption as a simple and powerful model. The steps in replication, the viral initiator, the host proteins, and their mechanisms of action were initially defined using a cell-free SV40 replication reaction. Although our understanding of the vastly more complex host replication fork is advancing, no eukaryotic replisome has yet been reconstituted and the SV40 paradigm remains a point of reference. This article reviews some of the milestones in the development of this paradigm and speculates on its potential utility to address unsolved questions in eukaryotic genome maintenance.

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Figures

Figure 1
Figure 1
Electron micrograph of an SV40 minichromosome isolated from productively infected cells. (Scale bar 100 nm). (Reprinted from (Griffith, 1975) with permission from AAAS.)
Figure 2
Figure 2
Daniel Nathans (left) and Hamilton Smith in the laboratory at Johns Hopkins University. (Reprinted from (Roberts, 2005) with permission from Copyright 2005 National Academy of Sciences, U.S.A.)
Figure 3
Figure 3
Peter Tegtmeyer (left) in discussion at a DNA Tumor Virus meeting, University of Wisconsin-Madison (Courtesy of K. Rundell).
Figure 4
Figure 4
Rolf Knippers in his laboratory at the University of Konstanz, Germany, in the 1980’s. (Courtesy of M. Baack).
Figure 5
Figure 5
Active unwinding from the SV40 origin by a Tag double hexamer. Tag was incubated under unwinding conditions with a duplex plasmid DNA fragment containing the SV40 origin 1.1 or 1.5 kb from the ends. The reaction was terminated by glutaraldehyde, the sample was purified, spread, negatively stained, and visualized by electron microscopy. Two single-stranded loops bound to single-stranded DNA binding protein. emanate from a Tag double hexamer (see inset). (Scale bar 100 nm) The double hexamer and the loops dissociated into a theta-like structure after treatment with EDTA (not shown). (Reprinted from (Wessel, Schweizer, and Stahl, 1992) with permission from Copyright 1992 American Society for Microbiology.)
Figure 6
Figure 6
Thomas J. Kelly (left) and Bruce Stillman (right) at a reception during the 1994 Cold Spring Harbor Symposium (Courtesy of Cold Spring Harbor Archives).
Figure 7
Figure 7
A minimal set of replication proteins at a eukaryotic fork. MCM helicase substitutes here for Tag; the PCNA clamp loader RFC and topoisomerases are not shown. (Reprinted from (Garg and Burgers, 2005) with permission from Copyright 2005 Taylor & Francis.)
Figure 8
Figure 8
Linking the polymerase switch to Okazaki fragment processing. The mechanism of elongation of a primed DNA template on the leading strand or for each Okazaki fragment on the lagging strand was studied in reactions reconstituted with purified proteins (steps 1–4). The mechanism of Okazaki fragment maturation was also elucidated in reconstituted reactions (steps 5–7). (Reprinted from (Waga and Stillman, 1998) with permission from Annual Reviews.) (For a current view of Okazaki fragment processing, see (Rossi et al., 2008))
Figure 9
Figure 9
Modular organization of Tag domains and linkers. Atomic structures of DnaJ (Kim, Ahn, and Cho, 2001), OBD (Luo et al., 1996), and helicase (Zn and ATPase/AAA+) domains (Li et al., 2003) are shown approximately to scale with the intervening peptides as dotted lines. The structure of the host-range domain has not been determined. (Courtesy of X.S. Chen.)
Figure 10
Figure 10
Crystallographer Xiaojiang S. Chen, University of Southern California.
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