Obsolete models of DNA structure: Difference between revisions

Revision as of 08:44, 16 July 2021

Revision as of 03:33, 12 September 2021

Line 19:

| journal=[[Experientia]] |volume=6 |issue=6 |pages=201–209 |doi=10.1007/BF02173653 |pmid=15421335

|s2cid=2522535

}}</ref> Prior to this, X-ray data being gathered in the 1950s indicated that DNA formed some sort of helix, but it had not yet been discovered what the exact structure of that helix was. There were therefore several proposed structures that were later overturned by the data supporting a DNA duplex. The most famous of these early models was by [[Linus Pauling]] and [[Robert Corey|Roberyt Corey]] in 1953 in which they proposed a triple helix with the phosphate backbone on the inside, and the nucleotide bases pointing outwards.<ref>{{cite journal|vauthors=Pauling L, Corey RB|date=February 1953|title=A Proposed Structure For The Nucleic Acids|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=39|issue=2|pages=84–97|doi=10.1073/pnas.39.2.84|pmc=1063734|pmid=16578429|bibcode=1953PNAS...39...84P|doi-access=free}}</ref><ref>{{cite journal|vauthors=Pauling L, Corey RB|date=February 1953|title=Structure of the nucleic acids|journal=Nature|volume=171|issue=4347|pages=346|doi=10.1038/171346a0|pmid=13036888|bibcode=1953Natur.171..346P|s2cid=4151877|doi-access=free}}</ref> A broadly similar, but detailed structure was also proposed by Bruce Fraser that same year.<ref>{{cite journal|url=http://scarc.library.oregonstate.edu/coll/pauling/dna/notes/fraser-structure.html|title=The Structure of Deoxyribose Nucleic Acid|last=Fraser|first=Bruce|date=1953|journal=Journal of Structural Biology|volume=145|issue=3|pages=184–5|doi=10.1016/j.jsb.2004.01.001|pmid=14997898|name-list-style=vanc}}</ref> However, Watson and Crick soon identified several problems with these models:

* Negatively charged phosphates near the axis repel each other, leaving the question of how the three-chain structure stays together.

Line 29:

=== Before the discovery of topoisomerases ===

[[File:Wu non-helical DNA structure.ogv|thumb|200px|Linear tetraplex model proposal (1969)<ref name=":0">{{Cite journal|last=Wu|first=Tai Te|year=1969|title=Secondary Structures of DNA|journal=[[Proceedings of the National Academy of Sciences]]|volume=63|issue=2|pages=400–405|doi=10.1073/pnas.63.2.400|issn=0027-8424|pmid=5257129|pmc=223578|doi-access=free}}</ref>]]Even once the DNA duplex structure was solved, it was initially an open question whether additional DNA structures were needed to explain its overall topology. there were initially questions about how it might affect DNA replication. In 1963, [[autoradiograph]]s of the [[Circular prokaryote chromosome|''E. coli'' chromosome]] demonstrated that it was a [[Circular prokaryote chromosome|single circular molecule]] that is replicated at a pair of [[replication fork]]s at which both new DNA strands are being synthesized.<ref name="Cairns_1963">{{cite journal | last = Cairns | first = J. | title = The bacterial chromosome and its manner of replication as seen by autoradiography | journal = [[J. Mol. Biol.]] | volume = 6 | issue = 3| pages = 208–13 |year = 1963 | pmid = 14017761 | doi = 10.1016/s0022-2836(63)80070-4}}</ref> The two daughter chromosomes after replication would therefore be topologically linked. The separation of the two linked daughter DNA strands during replication either required DNA to have a net-zero helical twist, or for the strands to be cut, crossed, and rejoined. It was this apparent contradictions that early non-helical models attempted to address until the discovery of [[topoisomerases]] in 1970 resolved the problem.<ref name="Biegeleisen_2002">{{cite journal|author=Biegeleisen K|year=2002|title=Topologically non-linked circular duplex DNA|journal=[[Bull. Math. Biol.]]|volume=64|issue=3|pages=589–609|citeseerx=10.1.1.573.5418|doi=10.1006/bulm.2002.0288|pmid=12094410|s2cid=13269612}}</ref><ref>{{Cite journal|last=Wang|first=J. C.|author-link=James C. Wang|year=2002|title=Cellular roles of DNA topoisomerases: a molecular perspective|journal=Nature Reviews Molecular Cell Biology|volume=3|issue=6|pages=430–440|doi=10.1038/nrm831|issn=1471-0072|pmid=12042765|s2cid=205496065}}</ref>

In the 1960s and 1970s, a number of structures were hypothesised that would give a net-zero helical twist over the length of the DNA, either by being fully straight throughout or by alternating right-handed and left-handed helical twists.<ref name="Rodley_1976">{{cite journal|vauthors=Rodley GA, Scobie RS, Bates RH, Lewitt RM|year=1976|title=A possible conformation for double-stranded polynucleotides|journal=[[Proc. Natl. Acad. Sci. U.S.A.]]|volume=73|issue=9|pages=2959–63|bibcode=1976PNAS...73.2959R|doi=10.1073/pnas.73.9.2959|pmc=430891|pmid=1067594|doi-access=free}}</ref><ref name="sasisekharan1">{{cite journal|last1 = Sasisekharan|first1 = V.|author-link1 = V. Sasisekharan|last2 = Pattabiraman|first2 = N.|year = 1976|journal = [[Curr. Sci.]]|volume = 45|pages = 779–783|title = Double standard polynucleotides: Two typical alternative conformations for nucleic acids|url = https://www.currentscience.ac.in/cs/Downloads/article_id_045_22_0779_0783_0.pdf}}</ref> For example, in 1969, a linear tetramer structure was hypothesised,<ref name=":0" /> and in 1976, a structure with alternating sections of right-handed and left-handed helix was independently proposed by two different groups.<ref>{{Cite journal|last1=Sasisekharan|first1=V.|last2=Pattabiraman|first2=N.|year=1976|title=Double stranded polynucleotides: two typical alternative conformations for nucleic acids|journal=[[Current Science]]|volume=45|pages=779–783|author-link1=V. Sasisekharan}}</ref><ref name="Sasisekharan_1978">{{cite journal|last1=Sasisekharan|first1=V.|last2=Pattabiraman|first2=N.|last3=Gupta|first3=G.|year=1978|title=Some implications of an alternative structure for DNA|journal=[[Proc. Natl. Acad. Sci. U.S.A.]]|volume=75|issue=9|pages=4092–6|bibcode=1978PNAS...75.4092S|doi=10.1073/pnas.75.9.4092|pmc=336057|pmid=279899|author-link1=V. Sasisekharan|doi-access=free}}</ref> The alternating twists model was initially presented with the helicity changing every half turn, but later long stretches of each helical direction were later proposed.<ref>{{Cite journal|last1=Rodley|first1=G. A.|year=1995|title=Reconsideration of some results for linear and circular DNA|journal=[[Journal of Biosciences]]|volume=20|issue=2|pages=245–257|doi=10.1007/BF02703272|s2cid=40531350}}</ref> However, these models suffered from a lack of experimental support.<ref name="Crick_1979">{{cite journal|last1=Crick|first1=F. H.|last2=Wang|first2=J. C.|author-link2=James C. Wang|last3=Bauer|first3=W. R.|year=1979|title=Is DNA really a double helix?|url=http://profiles.nlm.nih.gov/ps/access/SCBCDD.pdf|journal=[[J. Mol. Biol.]]|volume=129|issue=3|pages=449–457|doi=10.1016/0022-2836(79)90506-0|pmid=458852|author-link1=Francis Crick}}</ref> Under torsional stress, a [[Z-DNA]] structure can form with opposite twist to B-form DNA, but this is rare within the cellular environment.<ref>{{Cite journal|last1=Rich|first1=Alexander|last2=Zhang|first2=Shuguang|date=2003|title=Z-DNA: the long road to biological function|journal=Nature Reviews Genetics|language=en|volume=4|issue=7|pages=566–572|doi=10.1038/nrg1115|pmid=12838348|s2cid=835548|issn=1471-0064}}</ref> The discovery of [[topoisomerase]]s and [[gyrase]]s, enzymes that can change the linking number of circular nucleic acids and thus "unwind" and "rewind" the replicating bacterial chromosome, solved the topological objections to the B-form DNA helical structure.<ref>{{Cite journal|last1=Keszthelyi|first1=Andrea|last2=Minchell|first2=Nicola|last3=Baxter|first3=Jonathan|year=2016|title=The Causes and Consequences of Topological Stress during DNA Replication|journal=[[Genes (journal)|Genes]]|volume=7|issue=12|pages=134|doi=10.3390/genes7120134|pmid=28009828|issn=2073-4425|pmc=5192510|doi-access=free}}</ref> Indeed, in the absence of these topology-altering enzymes, small circular viral and plasmid DNA ''are'' inseparable supporting structure whose strands are topologically locked together.<ref name="Vinograd_1965">{{cite journal|vauthors=Vinograd J, Lebowitz J, Radloff R, Watson R, Laipis P|year=1965|title=The twisted circular form of polyoma viral DNA|journal=[[Proc. Natl. Acad. Sci. U.S.A.]]|volume=53|issue=5|pages=1104–11|bibcode=1965PNAS...53.1104V|doi=10.1073/pnas.53.5.1104|pmc=301380|pmid=4287964|doi-access=free}}</ref>

Non-helical DNA proposals have therefore dropped from mainstream science.<ref name="gautham" /><ref name="Biegeleisen_2002" />[[File:Rodley Side-By-Side DNA structure.ogv|thumb|200px|Side-By-Side model structure proposal (1976)<ref name="Rodley_1976" />]]

=== Confirmation of helical structure ===

Initially, there had been questions of whether the solved DNA structures were artefacts of the X-ray crystallography techniques used. However, the structure of DNA was subsequently confirmed in solution via gel electrophoretic methods<ref>{{Cite journal|last=Wang|first=J. C.|author-link=James C. Wang|year=1979|title=Helical repeat of DNA in solution|journal=[[Proceedings of the National Academy of Sciences]]|volume=76|issue=1|pages=200–203|doi=10.1073/pnas.76.1.200|issn=0027-8424|pmid=284332|pmc=382905|bibcode=1979PNAS...76..200W|doi-access=free}}</ref> and later via [[Nuclear magnetic resonance spectroscopy of proteins|solution NMR]]<ref>{{Cite journal|last1=Ghosh|first1=Anirban|last2=Kar|first2=Rajiv Kumar|last3=Jana|first3=Jagannath|last4=Saha|first4=Abhijit|last5=Jana|first5=Batakrishna|last6=Krishnamoorthy|first6=Janarthanan|last7=Kumar|first7=Dinesh|last8=Ghosh|first8=Surajit|last9=Chatterjee|first9=Subhrangsu|year=2014|title=Indolicidin Targets Duplex DNA: Structural and Mechanistic Insight through a Combination of Spectroscopy and Microscopy|journal=[[ChemMedChem]]|volume=9|issue=9|pages=2052–2058|doi=10.1002/cmdc.201402215|pmid=25044630|issn=1860-7179|hdl=2027.42/108345|s2cid=33138700|hdl-access=free}}</ref> and [[Atomic force microscopy|AFM]]<ref>{{Cite journal|last1=Pyne|first1=Alice|last2=Thompson|first2=Ruth|last3=Leung|first3=Carl|last4=Roy|first4=Debdulal|last5=Hoogenboom|first5=Bart W.|date=2014|title=Single-Molecule Reconstruction of Oligonucleotide Secondary Structure by Atomic Force Microscopy|journal=Small|volume=10|issue=16|pages=3257–3261|doi=10.1002/smll.201400265|pmid=24740866|issn=1613-6829|url=http://discovery.ucl.ac.uk/1427322/1/smll201400265.pdf}}</ref> indicating that the crystallography process did not distort it. The structure of DNA in complex with [[nucleosome]]s, [[helicase]]s, and numerous other [[DNA binding protein]]s also supported its biological relevance ''in vivo''.<ref>{{Cite journal|last1=Morgunova|first1=E.|last2=Taipale|first2=J.|year=2017|title=Structural perspective of cooperative transcription factor binding|journal=[[Current Opinion in Structural Biology]]|series=Protein–nucleic acid interactions • Catalysis and regulation|volume=47|pages=1–8|doi=10.1016/j.sbi.2017.03.006|pmid=28349863|issn=0959-440X|doi-access=free}}</ref>

==References==