Why is it that DNA strands are running in anti-parallel fashion? Given the chemical base-pairing, they could have been parallel just as well.

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    $\begingroup$ How could they run parallel instead of anti-parallel when they need to be complementary to each other, and at the same time have the same structure? Having them parallel and complementary would need them to be enantiomers, and that's biochemically a huge mess. I'm not posting it as answer because I can't really justify it $\endgroup$ – Athe Aug 21 '15 at 13:38
  • $\begingroup$ This is a similar question in Biology SE biology.stackexchange.com/questions/27839/… $\endgroup$ – falsum Aug 22 '15 at 2:09

Parallel nucleic acid double strand is possible but it is not as stable as the antiparallel form (Szabat and Kierzek, 2017). This is because the nucleobases are not in are not aligned in a way that is conducive for the Watson-Crick (WC) type base pairing. In parallel conformation, the bases can form Hoogsteen (HS) and reverse Watson-Crick (RWC) type base pairing (see below).

enter image description here

You can see that these base pairs are not as strong as that in WC base pairing:

  • No triple bond between G and C in RWC base pairing
  • GC pair occurs in HS base pairing only when C is protonated at low pH

Formation of parallel helices, therefore depends on the sequence.

In general, the formation of duplexes with parallel strand orientation is determined mostly by the sequence context and pH conditions. Fragments of RNA or DNA capable of forming a parallel duplex are often rich in A and C, which is related to their ability to become protonated, in middle acidic conditions.

However, it is not as simple as RNA/DNA base pairing with its complement. Parallel helices would not follow the WC base pairing rules and therefore predicting whether they will form is not that straightforward. However, parallel helices can form in vivo (see references 23–25 of Szabat and Kierzek, 2017).

You can also check out this article by Leontis et al. (2002) for hydrogen bond patterns in parallel and antiparallel helices.


This is more chemistry than Biology.

Both strands of DNA are 5' to 3' direction. Why so? because the direction is determined in terms of the direction in which purine or pyrimidine bases are added.

The four bases that exist in DNA are Adenine, Guanine, Thymine and Cytosine. They are referenced under Purine and Pyrimidine links posted above.

This molecule is added to the end of a new DNA molecule. It will be added to the 3' end of a new growing DNA molecule.

Skeletal formula of ATP
"Adenosintriphosphat protoniert" by NEUROtiker - Own work. Licensed under Public Domain via Commons.

What is the 3' and 5' end? Deoxyribose and Ribose sugar

The ribose sugar at position two will lose the OH, the 5' position is the one where the long chain of phosphates are added in the top image and this phosphate at position 5' will be bonded to the OH at position 3' seen in the deoxyribose molecule, this reaction will generate a phosphodiester bond.

Phosphodiester Bond Diagram.svg
"Phosphodiester Bond Diagram" by File:Enlace fosfodiéster.png, File:PhosphodiesterBondDiagram.png: User:G3pro (talk) Original uploader was User:G3pro at en.wikipedia.org Derivative work: User:Merops (talk) Derivative work: User:Deneapol (talk) Derivative work: User:KES47 (talk) Text tweaks: Incnis Mrsi (talk) Text tweaks: DMacks (talk)) - File:Enlace fosfodiéster.png. Licensed under CC BY-SA 3.0 via Commons.

And here's the complete reaction

phosphodiester linkage

If you have noticed the negative charge on the Oxygen, then you will notice that Oxygen has one more electron to donate for a covalent linkage. So this electron attacks the O-H bond at the 3' OH of the deoxy-ribose sugar to generate the phosphodiester bond.

So the 3' OH is always a requirement for addition of new bases to a DNA strand. The 5' refers to the dangling 5' end of the first Phosphate, while the 3' refers to the 3' OH of the Ribose sugar at the last base of the DNA. The entire reaction is catalysed by DNA Polymerase

P.S. They are not really free, there are many modifications which make them inert.

So that is why DNA is anti-parallel.

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    $\begingroup$ This answers why DNA strand have polarity but not why they form anti-parallel helices. $\endgroup$ – canadianer Aug 21 '15 at 15:19
  • $\begingroup$ Is there any other way in which DNA polymerase can polymerize the polymerization reaction? $\endgroup$ – FoldedChromatin Aug 21 '15 at 15:23
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    $\begingroup$ Nucleic acids must be added to the 3' OH forming the phosphodiester bond, which is the basis for 5' to 3' direction of DNA, there must always be a 3' OH to add more bases to which is why a Primer is added during replication, or else DNA will not have been replicated, so is that not reason enough for anti-parallelism? $\endgroup$ – FoldedChromatin Aug 21 '15 at 15:33

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