DNA Replication: The Rolling Circle Model

Gilbert, Walter; Dressler, David

doi:10.1101/sqb.1968.033.01.055

Cited by 385 publications

(132 citation statements)

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“…This result could not be reconciled with any model of DNA replication that involves only one origin of DNA synthesis (9,10). The existence of multiple sites of initiation of DNA synthesis in T4 DNA also corroborates our previous results (11), which show that multiple linkages exist between replicating T4 DNA and a set of proteinaceous units that might represent the replicating machinery.…”

Section: Multiple Initiation Sitessupporting

confidence: 75%

Structure of the Replicating DNA from Bacteriophage T4

Delius

Howe

Kozinski

1971

Proc. Natl. Acad. Sci. U.S.A.

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At an early stage of replication, parental T4 DNA shows a loop structure often displaying two 3'-ended, single-stranded "whiskers", located in trans configuration at the branching-points. Several Replicative loops were first demonstrated by Cairns in the DNA of Escherichia coli (1). Schnos and Inman showed that the replication of lambda DNA always starts at the same place on the DNA molecule, and usually proceeds from that site in both directions (2).We showed that partially replicated molecules of T4 DNA that have not yet completed one round of replication cannot be resolved by shearing into pure parental and hybrid moieties, which suggests that multiple initiation occurs (3). In this paper we describe the results of an electron microscopic study of the partially replicated from of replicating T4 DNA.

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Section: Multiple Initiation Sitessupporting

confidence: 75%

Structure of the Replicating DNA from Bacteriophage T4

Delius

Howe

Kozinski

1971

Proc. Natl. Acad. Sci. U.S.A.

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“…This term implies that these structures can produce linear SV40 multimers by analogy with bacteriophage rolling-circle forms (5). The evidence for rolling circles with multimeric tails in normal lytic infections rests on a few observations of very rare molecules in Hirt extracts of infected cells (1).…”

Section: Discussionmentioning

confidence: 99%

Topoisomerase inhibitors can selectively interfere with different stages of simian virus 40 DNA replication.

Snapka¹

1986

Mol. Cell. Biol.

119

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I have found that antineoplastic drugs which are known to be inhibitors of mammalian DNA topoisomerases have pronounced and selective effects on simian virus 40 DNA replication. Ellipticine, 4'-(9-acridinylamino)methanesulfon-m-aniside, and Adriamycin blocked decatenation of newly replicated simian virus 40 daughter chromosomes in vivo. The arrested decatenation intermediates produced by these drugs contained single-strand DNA breaks. Ellipticine in particular produced these catenated dimers rapidly and efficiently. Removal of the drug resulted in rapid reversal of the block and completion of decatenation. The demonstration that these drugs interfere with decatenation suggests that they may exert their cytotoxic and antineoplastic effects by preventing the separation of newly replicated cellular chromosomes. Camptothecin rapidly breaks replication forks in growing Cairns structures. It is likely that the target of camptothecin is the "swivel" topoisomerase required for DNA replication and that it is located at or very near the replication fork in vivo. Evidence is presented that many of the broken Cairns structures are in fact half-completed sister chromatid exchanges. One pathway for the resolution of these structures is completion of the sister chromatid exchange to produce a circular head-to-tail dimer.DNA topoisomerases are now recognized as important targets for cancer chemotherapy (for reviews, see references 20 and 32). A number of cytotoxic drugs which were found to have antineoplastic properties have recently been shown to be topoisomerase inhibitors (3,12,15,25,26,31,33). These drugs typically interfere with the breakage-reunion cycles of topoisomerases to produce single-and double-strand DNA breaks. Recent studies have shown a correlation between cytotoxicity and levels of DNA strand breakage caused by these drugs (6,7,21). It is also possible that these drugs can exert their cytotoxic and antineoplastic effects through interference with reactions that require topoisomerases, such as replication fork progression, transcription, and separation (decatenation) of newly replicated daughter chromosomes. The work reported here demonstrates that topoisomerase inhibitors can selectively and reversibly interfere either with replication forks or with the decatenation process in simian virus 40 (SV40) DNA replication. Improved understanding of the modes of action of this class of drugs should aid in the rational design of a second generation of antineoplastic topoisomerase inhibitors.MATERIALS AND METHODS Cell culture and virus infection. African green monkey kidney cells (CV-1) were grown in Eagle minimal essential medium (Gibco) supplemented with 14 mM HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, pH 7.2) and 4 mM NaHCO3. Cells were infected with SV40 strain 777 at a multiplicity of 10 PFU/cell, and experiments were carried out 36 h after infection at the peak of SV40 DNA replication.Radiolabeling and preparation of viral DNA. Replicating SV40 DNA was pulse-labeled with [methyl-3H]thymidine as in...

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“…Some of the single strands obtained by denaturing this heterogeneous component sediment faster than VS, as predicted by the rolling-circle model (73). Only the VS of the newly made RF II is nicked, and only the VS is chased from RF II into a single strand.…”

Section: Dna Replicationmentioning

confidence: 69%

“…The mechanical problems involved in semiconservative replication of a circular duplex DNA molecule have been discussed by many authors (38,39,51,55,73,100,111,122,139,178,188,202). The replicating molecule has two discontinuities, the growth point and the origin (Fig.…”

Section: Dna Replicationmentioning

confidence: 99%