Editing Semiconservative replication

{{Short description|Mechanism of DNA replication}}
'''Semiconservative replication''' describes the mechanism of [[DNA replication]] in all known cells. DNA replication occurs on multiple [[Origin of replication|origins of replication]] along the DNA template strands. 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.<ref>{{cite journal | vauthors = Ekundayo B, Bleichert F | title = Origins of DNA replication | journal = PLOS Genetics | volume = 15 | issue = 9 | pages = e1008320 | date = September 2019 | pmid = 31513569 | pmc = 6742236 | doi = 10.1371/journal.pgen.1008320 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Pray, Leslie A | title = Semi-conservative DNA replication: Meselson and Stahl | journal = Nature Education | volume = 1(1):98 }}</ref> 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.<ref name="Griffiths_1999">{{cite book|title=An Introduction to Genetic Analysis|vauthors=Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart WM |publisher=W.H. Freeman |year=1999 |isbn=978-0-7167-3520-5 |location=San Francisco |chapter=Chapter 8: The Structure and Replication of DNA |chapter-url= https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.1505 }}</ref><ref name="Meselson_1958">{{cite journal | vauthors = Meselson M, Stahl FW | title = The Replication of DNA in Escherichia Coli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 44 | issue = 7 | pages = 671–82 | date = July 1958 | pmid = 16590258 | pmc = 528642 | doi = 10.1073/pnas.44.7.671 | bibcode = 1958PNAS...44..671M | doi-access = free }}</ref>

== Discovery ==

[[File:Meselson-stahl_experiment_diagram_en.svg|alt=|thumb|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]],<ref name="Meselson_1958" /><ref>{{cite book|title=Phage and the Origins of Molecular Biology|vauthors=Meselson M, Stahl FW|date=2007|publisher=Cold Spring Harbor Laboratory Press|isbn=978-0-87969-800-3|veditors=Cairns J, Stent GS, Watson JD|location=Cold Spring Harbor|chapter=Demonstration of the semiconservative mode of DNA duplication.}}</ref> which confirmed that DNA replicated semi-conservatively by conducting an experiment using two [[isotopes]]: [[Nitrogen 15|nitrogen-15]] ({{SimpleNuclide|Nitrogen|15}}) and [[Nitrogen 14|nitrogen-14]] ({{SimpleNuclide|Nitrogen|}}). When {{SimpleNuclide|Nitrogen|}} was added to the heavy {{SimpleNuclide|Nitrogen|15}}-{{SimpleNuclide|Nitrogen|15}} DNA, a hybrid of {{SimpleNuclide|Nitrogen|15}}-{{SimpleNuclide|Nitrogen|}} was seen in the first generation. After the second generation, the hybrid remained, but light DNA ({{SimpleNuclide|Nitrogen|}}-{{SimpleNuclide|Nitrogen|}}) 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.<ref>{{cite journal | vauthors = Hanawalt PC | title = Density matters: the semiconservative replication of DNA | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 52 | pages = 17889–94 | date = December 2004 | pmid = 15608066 | doi = 10.1073/pnas.0407539101 | doi-access = free | pmc = 539797 }}</ref>

== Nature of DNA replication ==
[[Image:DNAreplicationModes.png|thumb|300px|left|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<ref name="Griffiths_1999" /><ref name="Meselson_1958" />for [[DNA replication]]:

* Semiconservative replication would produce two copies that each contained one of the original strands of DNA and one new strand.<ref name="Griffiths_1999" />Semiconservative replication is beneficial to DNA repair. During replication, the new strand of DNA adjusts to the modifications made on the template strand.<ref name="Norris_2019">{{cite journal | vauthors = Norris V | title = Does the Semiconservative Nature of DNA Replication Facilitate Coherent Phenotypic Diversity? | journal = Journal of Bacteriology | volume = 201 | issue = 12 | date = June 2019 | pmid = 30936370 | pmc = 6531617 | doi = 10.1128/jb.00119-19 }}</ref>
* 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.<ref name="Griffiths_1999" />
* 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.<ref name="Griffiths_1999" /> 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.<ref name = "Watson_2014" />

== Separation and recombination of double-stranded DNA ==
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 I topoisomerase|Type IA Topoisomerase]], [[Type I topoisomerase|Type IB Topoisomerase]], and [[Type II topoisomerase|Type II Topoisomerase]].<ref>{{cite book |last=Brown |first=Terence A. | name-list-style = vanc | chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK21113/ |chapter = Genome Replication | title = Genomes | edition = 2nd|date=2002|publisher=Wiley-Liss }}</ref> Type I Topoisomerase unwinds double stranded DNA while Type II Topoisomerase breaks the [[hydrogen bond]]s linking the complementary base pairs of DNA.<ref name = "Watson_2014">{{cite book | first1 = James D | last1 = Watson | first2 = Alexander | last2 = Gann | first3 = Tania A | last3 = Baker | first4 = Michael | last4 = Levine | first5 = Stephen P | last5 = Bell | first6 = Richard | last6 = Losick | name-list-style = vanc | date = 2014 |title=Molecular Biology of the Gene |isbn=978-0-321-76243-6 |edition=Seventh |location=Boston |oclc=824087979}}</ref>

== Rate and accuracy ==
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''.<ref>{{cite journal | vauthors = McCarthy D, Minner C, Bernstein H, Bernstein C | title = DNA elongation rates and growing point distributions of wild-type phage T4 and a DNA-delay amber mutant | journal = Journal of Molecular Biology | volume = 106 | issue = 4 | pages = 963–81 | date = October 1976 | pmid = 789903 | doi = 10.1016/0022-2836(76)90346-6 }}</ref>  During the period of exponential DNA increase at 37&nbsp;°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 {{val|2.4|e=−8}}.<ref name="pmid9560386">{{cite journal | vauthors = Drake JW, Charlesworth B, Charlesworth D, Crow JF | title = Rates of spontaneous mutation | journal = Genetics | volume = 148 | issue = 4 | pages = 1667–86 | date = April 1998 | doi = 10.1093/genetics/148.4.1667 | pmid = 9560386 | pmc = 1460098 }}</ref>  Thus, semiconservative DNA replication is both rapid and accurate.

== Applications ==
Semiconservative replication provides many advantages for DNA. It is fast, accurate, and allows for easy repair of DNA. It is also responsible for [[Phenotype|phenotypic]] diversity in a few prokaryotic species.<ref>{{cite journal|vauthors=McCarthy D, Minner C, Bernstein H, Bernstein C|date=October 1976|title=DNA elongation rates and growing point distributions of wild-type phage T4 and a DNA-delay amber mutant|journal=Journal of Molecular Biology|volume=106|issue=4|pages=963–81|doi=10.1016/0022-2836(76)90346-6|pmid=789903}}</ref> The process of creating a newly synthesized strand from the template strand allows for the old strand to be [[Methylation|methylated]] at a separate time from the new strand. This allows repair enzymes to proofread the new strand and correct any [[mutation]]s or errors.<ref name="Norris_2019" />

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.<ref name="Norris_2019" />

== See also ==
*[[Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid]]
*[[DNA replication]]

== References ==
{{Reflist|32em}}

[[Category:DNA replication]]