Do histones have to be synthesized before DNA is replicated to allow the DNA to coil around histones?

  • $\begingroup$ Only nucleic acids are replicated — proteins are synthesized from mRNA. If you didn't know this you shouldn't have posted but done some preliminary work instead. However your basic question on the coordination of DNA and histone synthesis is worth asking, so I have edited your question appropriately. $\endgroup$
    – David
    Commented May 7, 2017 at 20:01
  • 1
    $\begingroup$ I love this question the way it is. $\endgroup$ Commented Jul 26, 2017 at 19:17

2 Answers 2


Yes, they have to. But that is just half of the story.

The (canonical) histones which are used in DNA replication are synthesized at the beginning of the S phase, and subsequently transported into the nucleus. Studies have shown that newly synthesized DNA is immediately packed into nucleosomes. Thus, it is necessary that these structures are available prior to (or at least just in time with) the replication.

However, there are different models on how the histones are inserted into new DNA. One model assumes that old and new nucleosomes are both incorporated into newly synthesized DNA after the replication fork. Others assume a semi-conservative approach where the old histones are disassembled into their subunits and then mixed together with the newly synthesized ones. For example, there is a model that proposes that the parental H2A/H2B and the H3/H4 dimers disassociate, while another assumes a disassociation of the H3/H4 dimers as well.

Figure: Nucleosome synthesis models for DNA replication enter image description here


a Angélique Galvani and Christophe Thiriet (2013). Replicating – DNA in the Refractory Chromatin Environment, The Mechanisms of DNA Replication, Dr. David Stuart (Ed.), InTech, DOI: 10.5772/52656. Available from: https://www.intechopen.com/books/the-mechanisms-of-dna-replication/replicating-dna-in-the-refractory-chromatin-environment


In Molecular Biology of the Cell (Chapter 4), it is written that

The major histones are synthesized primarily during the S phase of the cell cycle and assembled into nucleosomes on the daughter DNA helices just behind the replication fork (see Figure 5–32). In contrast, most histone variants are synthesized throughout interphase. They are often inserted into already-formed chromatin, which requires a histone-exchange process catalyzed by the ATP-dependent chromatin remodeling complexes discussed previously

  • $\begingroup$ This is too much simplified. Old histones are reused, and probably mixed together with new ones. $\endgroup$
    – adjan
    Commented May 16, 2017 at 16:43
  • $\begingroup$ @adjan You are right. If necessary I will put my answer as a community wiki in order to improve it with your explanation. Otherwise, we can leave them side by side. $\endgroup$
    – gc5
    Commented May 17, 2017 at 9:13

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