I've been solving some biology questions, and according to one of them ( I have the responses too) the following phrase is false:
"Both strands are always synthesised in the 5' to 3' direction."
How can this be? From what I know DNA is always read from 3' to 5', and synthesised from 5' to 3'.
When is DNA not synthesized from 5' to 3'?

  • 2
    $\begingroup$ What do you mean “how can that be?”? That’s the way it is. Deoxy-ribose is not symmetrical. Enzymes have substrate specificity. And plasmids have no bearing on the matter. Search for Berg on NCBI Bookshelf, and read the section on DNA synthesis. Pay careful attention to the chemistry. $\endgroup$
    – David
    May 5, 2021 at 19:27
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    $\begingroup$ I have looked trough the book you have recommended me, and it still did not give me the response I needed. According to this book "At a replication fork, both strands are synthesized in a 5′ → 3′ direction.". Which I agree with, my question was why according to my book, it says that it is false that strands are always synthesized like that. Unless, it was referring to the direction of growth, in which case the lagging strand grows in the 3' to 5' direction, but it doesn't because my book uses the word "synthesized" not "grow". This is where my confusion comes from. $\endgroup$
    – Francesca
    May 6, 2021 at 9:17
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    $\begingroup$ Am I right in thinking your concern is as follows? All known DNA polymerases add NTPs to the 3'-OH of the deoxy-ribose so that the direction of synthesis is 5′ → 3. In most organisms the two strands grow in both directions by a complex mechanism at the replication fork involving RNA primers and Okazaki fragments etc. However small circular genomes use a different mechanism — the rolling circle mechanism (described in Wikipedia etc.) — in which growth is just in a single direction. If so, and you still have a question about this, could you clarify what your question is. $\endgroup$
    – David
    May 6, 2021 at 13:43

1 Answer 1


It sounds like your guess was right and the exception is the lagging strand. The statement is phrased poorly, but it seems like they were going for the lagging strand. Either they meant for you to think that
-the lagging strand is growing 3' to 5'
or, more likely,
-the polymerase is only synthesizing on one (leading) strand at a time

While technically the book was correct, it was a trick question and phrased unfairly.

You are completely right that DNA is synthesized from 5' to 3'. I don't know of any exceptions to this, but hesitate to say anything overly definitive because there are so many rare exceptions in science. I can say with some confidence that DNA polymerase cannot ever synthesize in the 3' -> 5' direction. If you haven't already, I highly recommend checking out the Khan Academy article, Molecular mechanism of DNA replication! Nature Education also has a pretty good article on the topic, Major Molecular Events of DNA Replication.

  • $\begingroup$ I don’t even think the book was technically correct. It’s odd to say that DNA synthesis occurs 3’ to 5’ even if you are referring to lagging strand growth. $\endgroup$
    – canadianer
    May 22, 2021 at 0:41
  • $\begingroup$ I agree completely, I was trying to cover all the bases since it's so unclear what the book was going for. I edited my answer so hopefully it's a little more clear though! $\endgroup$
    – Catherine
    May 23, 2021 at 1:29
  • $\begingroup$ text books are rarely written by relevant scientists, the person who wrote the question probably did not understand it. $\endgroup$
    – John
    May 24, 2021 at 14:15

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