Semiconservative replication

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Semiconservative replication describes the mechanism of DNA replication in all known cells. DNA replication occurs on multiple origins of replication along the DNA template strand. As the DNA double helix is unwound by helicase, replication occurs separately on each template strand in antiparallel directions. This process is known as semi-conservative replication because two copies of the original DNA molecule are produced, each copy conserving (replicating) the information from one half of the original DNA molecule.[1] [2] Each copy contains one original strand and one newly-synthesized strand. (Both copies should be identical, but this is not entirely assured.) The structure of DNA (as deciphered by James D. Watson and Francis Crick in 1953) suggested that each strand of the double helix would serve as a template for synthesis of a new strand. It was not known how newly synthesized strands combined with template strands to form two double helical DNA molecules.[3][4]

Discovery[edit]

Meselson-Stahl experiment using isotopes to discover semiconservative replication.

Multiple experiments were conducted to determine how DNA replicates. The semiconservative model was anticipated by Nikolai Koltsov and later supported by the Meselson-Stahl experiment.,[4][5] which confirmed that DNA replicated semi-conservatively by conducting an experiment using two isotopes: nitrogen-15 (15
N
) and nitrogen-14 (14
N
). When 14
N
was added to the heavy 15
N
-15
N
DNA, a hybrid of 15
N
-14
N
was seen in the first generation. After the second generation, the hybrid remained, but light DNA (14
N
-14
N
) was seen as well. This indicated that DNA replicated semi-conservatively. This mode of DNA replication allowed for each daughter strand to remain associated with its template strand.[6]

Models of replication[edit]

Three postulated methods of DNA synthesis

Semiconservative replication derives its name from the fact that this mechanism of transcription was one of three models originally proposed[3][4] for DNA replication:

  • Semiconservative replication would produce two copies that each contained one of the original strands of DNA and one new strand.[3] Semiconservative replication is beneficial to DNA repair. During replication, the new strand of DNA adjusts to the modifications made on the template strand.[7]
  • 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.[3]
  • 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.[3] The strands of DNA were originally thought to be broken at every tenth base pair to add the new DNA template. Eventually, all new DNA would make up the double helix after many generations of replication.[8]

Separation and recombination of double-stranded DNA[edit]

For semiconservative replication to occur, the DNA double-helix needs to be separated so the new template strand can be bound to the complementary base pairs. Topoisomerase is the enzyme that aids in the unzipping and recombination of the double-helix. Specifically, topoisomerase prevents the double-helix from supercoiling, or becoming too tightly wound. Three topoisomerase enzymes are involved in this process: Type IA Topoisomerase, Type IB Topoisomerase, and Type II Topoisomerase.[9] Type I Topoisomerase unwinds double stranded DNA while Type II Topoisomerase breaks the hydrogen bonds linking the complementary base pairs of DNA.[8]

Rate and accuracy[edit]

The rate of semiconservative DNA replication in a living cell was first measured as the rate of the T4 phage DNA strand elongation in phage-infected E. coli.[10] 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 2.4×10−8.[11] Thus, semiconservative DNA replication is both rapid and accurate.

Applications[edit]

Semiconservative replication provides many advantages for DNA. It is fast, accurate, and allows for easy repair of DNA. It is also responsible for phenotypic diversity in a few prokaryotic species.[12] The process of creating a newly synthesized strand from the template strand allows for the old strand to be methylated at a separate time from the new strand. This allows repair enzymes to proofread the new strand and correct any mutations or errors.[7]

DNA could have the ability to activate or deactivate certain areas on the newly synthesized strand that allows the phenotype of the cell to be changed. This could be advantageous for the cell because DNA could activate a more favorable phenotype to aid in survival. Due to natural selection, the more favorable phenotype would persist throughout the species. This gives rise to the idea of inheritance, or why certain phenotypes are inherited over another.[7]

See also[edit]

References[edit]

  1. ^ Ekundayo B, Bleichert F (September 2019). "Origins of DNA replication". PLOS Genetics. 15 (9): e1008320. doi:10.1371/journal.pgen.1008320. PMC 6742236. PMID 31513569.
  2. ^ Pray, Leslie A. "Semi-conservative DNA replication: Meselson and Stahl". Nature Education. 1(1):98.
  3. ^ a b c d e Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart WM (1999). "Chapter 8: The Structure and Replication of DNA". An Introduction to Genetic Analysis. San Francisco: W.H. Freeman. ISBN 978-0-7167-3520-5.
  4. ^ a b c Meselson M, Stahl FW (July 1958). "The Replication of DNA in Escherichia Coli". Proceedings of the National Academy of Sciences of the United States of America. 44 (7): 671–82. Bibcode:1958PNAS...44..671M. doi:10.1073/pnas.44.7.671. PMC 528642. PMID 16590258.
  5. ^ Meselson M, Stahl FW (2007). "Demonstration of the semiconservative mode of DNA duplication.". In Cairns J, Stent GS, Watson JD (eds.). Phage and the Origins of Molecular Biology. Cold Spring Harbor: Cold Spring Harbor Laboratory Press. ISBN 978-0-87969-800-3.
  6. ^ Hanawalt PC (December 2004). "Density matters: the semiconservative replication of DNA". Proceedings of the National Academy of Sciences of the United States of America. 101 (52): 17889–94. doi:10.1073/pnas.0407539101. PMC 539797. PMID 15608066.
  7. ^ a b c Norris V (June 2019). "Does the Semiconservative Nature of DNA Replication Facilitate Coherent Phenotypic Diversity?". Journal of Bacteriology. 201 (12). doi:10.1128/jb.00119-19. PMC 6531617. PMID 30936370.
  8. ^ a b Watson JD, Gann A, Baker TA, Levine M, Bell SP, Losick R (2014). Molecular Biology of the Gene (Seventh ed.). Boston. ISBN 978-0-321-76243-6. OCLC 824087979.
  9. ^ Brown TA (2002). "Genome Replication". Genomes (2nd ed.). Wiley-Liss.
  10. ^ 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". Journal of Molecular Biology. 106 (4): 963–81. doi:10.1016/0022-2836(76)90346-6. PMID 789903.
  11. ^ Drake JW, Charlesworth B, Charlesworth D, Crow JF (April 1998). "Rates of spontaneous mutation". Genetics. 148 (4): 1667–86. doi:10.1093/genetics/148.4.1667. PMC 1460098. PMID 9560386.
  12. ^ 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". Journal of Molecular Biology. 106 (4): 963–81. doi:10.1016/0022-2836(76)90346-6. PMID 789903.