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A summary of the three postulated methods of DNA synthesis

Semiconservative replication describes the mechanism by which DNA is replicated in all known cells. This mechanism of replication was one of three models originally proposed^[1] ^[2] for DNA replication:

Semiconservative replication would produce two copies that each contained one of the original strands and one new strand.
Conservative replication would leave the two original template DNA strands together in a double helix and would produce a copy composed of two new strands containing all of the new DNA base pairs.
Dispersive replication would produce two copies of the DNA, both containing distinct regions of DNA composed of either both original strands or both new strands.

The deciphering of the structure of DNA by Watson and Crick in 1953 suggested that each strand of the double helix would serve as a template for synthesis of a new strand. However, there was no way of knowing how the newly synthesized strands might combine with the template strands to form two double helical DNA molecules. The semiconservative model seemed most reasonable since it would allow each daughter strand to remain associated with its template strand. The semiconservative model was supported by the Meselson-Stahl experiment^[2]^[3] and other even more revealing experiments that allowed for autoradiographic visualization of the distribution of old and new strands within replicated chromosomes.

Experimental evidence confirmed that two lines were observed, therefore offering compelling evidence for the semi-conservative theory.

Rate and accuracy

The rate of semiconservative DNA replication in a living cell was first measured as the rate of phage T4 DNA strand elongation in phage-infected E. coli.^[4] During the period of exponential DNA increase at 37°C, the rate of strand elongation was 749 nucleotides per second. The mutation rate per base pair per round of replication during phage T4 DNA synthesis is 2.4 x 10⁻⁸.^[5] Thus semiconservative DNA replication is both rapid and accurate.

References

^ Anthony J. F. Griffiths et al. (1999). "8. The Structure and Replication of DNA". An Introduction to genetic analysis. San Francisco: W.H. Freeman. ISBN 0-7167-3520-2.
^ ^a ^b Meselson, M.; Stahl, F.W. (1958). "The Replication of DNA in Escherichia coli". PNAS 44: 671–82. doi:10.1073/pnas.44.7.671. PMC 528642. PMID 16590258.
^ Meselson M, Stahl FW. (2007 ) Demonstration of the semiconservative mode of DNA duplication. In “Phage and the Origins of Molecular Biology” (editors Cairns J, Stent GS, Watson JD). Cold Spring Harbor Laboratory Press ISBN 9780879698003
^ McCarthy D, Minner C, Bernstein H, Bernstein C (October 1976). "DNA elongation rates and growing point distributions of wild-type phage T4 and a DNA-delay amber mutant". J. Mol. Biol. 106 (4): 963–81. doi:10.1016/0022-2836(76)90346-6. PMID 789903.
^ Drake JW, Charlesworth B, Charlesworth D, Crow JF (April 1998). "Rates of spontaneous mutation". Genetics 148 (4): 1667–86. PMC 1460098. PMID 9560386.

English Journal

Heteroclitic Peptides Increase Proliferation and Reduce Evidence of Human Immunodeficiency Virus-Specific CD8⁺ T Cell Dysfunction.

Adegoke A1, Gladney K1, Gallant M1, Grant M1.
Viral immunology.Viral Immunol.2015 Oct;28(8):455-63. doi: 10.1089/vim.2015.0036. Epub 2015 Jul 31.
Human immunodeficiency virus (HIV)-specific CD8(+) T cell dysfunction parallels disease progression; therefore, restoring potent HIV-specific CD8(+) T cell responses is a key therapeutic goal. Certain CD8(+) T cell peptide epitope variants, termed heteroclitic, enhance cytokine production by the HIV
PMID 26230145

Analytical Ultracentrifugation and Its Role in Development and Research of Therapeutical Proteins.

Liu J1, Yadav S1, Andya J1, Demeule B1, Shire SJ2.
Methods in enzymology.Methods Enzymol.2015;562:441-76. doi: 10.1016/bs.mie.2015.04.008. Epub 2015 Aug 3.
The historical contributions of analytical ultracentrifugation (AUC) to modern biology and biotechnology drug development and research are discussed. AUC developed by Svedberg was used to show that proteins are actually large defined molecular entities and also provided the first experimental verifi
PMID 26412663

High-resolution analysis of Mammalian DNA replication units.

Chagin VO1, Reinhart M, Cardoso MC.
Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2015;1300:43-65. doi: 10.1007/978-1-4939-2596-4_3.
Genomic DNA of a eukaryotic cell is replicated once during the S-phase of the cell cycle to precisely maintain the complete genetic information. In the course of S-phase, semiconservative DNA synthesis is sequentially initiated and performed at thousands of discrete patches of the DNA helix termed r
PMID 25916704

Japanese Journal

2301 人工構造物における受動的な自己増殖の実現(要旨講演,一般セッション:マイクロナノ理工学)

松本光春,橋本周司
IIP情報・知能・精密機器部門講演会講演論文集 2008, 330-335, 2008-03-17
… It seems to us that one of the most successful examples of self-reproduction is the method used by deoxyribonucleic acid (DNA), that is, semiconservative replication. … Hence, we developed self reproducing structures by imitating the semiconservative replication of DNA. …
NAID 110007705061

A neo-darwinian algorithm : Asymmetrical mutations due to semiconservative DNA-type replication promote evolution

WADA K.
Proc. Natl. Acad. Sci. , USA 90, 11934-11938, 1993
NAID 30016295545

Effect of Antitumor Alkylating Agents on Semiconservative and Unscheduled DNA Syntheses in Rat Ascites Hepatoma Cells

奥本武城,今村博
Chemical & pharmaceutical bulletin 25(4), 812-814, 1977-04-25
… The effects of several compounds on ultraviolet light-induced unscheduled desoxyribonucleic acid (DNA) synthesis and semiconservative DNA synthesis were examined in rat ascites hepatoma, AH-44 cells. … The compounds used did not inhibit unscheduled DNA synthesis as much as or more than semiconservative DNA synthesis. … Only improsulfan had a tendency to inhibit unscheduled DNA synthesis to a greater extent than semiconservative DNA synthesis. …
NAID 110003622482