Two important properties about Histones:

  1. Too much or too little wrapping of DNA around histones inhibits and over-encourages DNA replication, respectively.

    The first observation is more easily understood through analogy. Imagine the story of Goldilocks, for example, whose porridge was either too cold, too hot, or just right. The same concept can be applied to histones and how they are wrapped with DNA. Basically, how tightly DNA is wrapped around a histone affects whether or not DNA polymerase can move along the DNA and replicate it so that the correct amount of DNA ends up in the divided cells.
    • "Too little" wrapped histones allow DNA polymerase (the enzyme that copies DNA) to move too quickly along the DNA, resulting in unnecessary replication and mutations in the copied DNA. It's the same as if you were rushing through your homework, for example, and you ended up getting the wrong answer or result. If DNA Polymerase rushes through DNA replication, the wrong nucleotides will be replicated, changing the result. Too Little Wrapping of Histones
    • "Too much" wrapped histones prevent DNA polymerase from reaching the DNA wrapped among the histone. Therefore the DNA cannot be replicated to put into the daughter cell after division. Likely, the daughter cell will die without the necessary DNA.
    • Too Much Wrapping of Histones
    • "Just right” wrapped histones allow DNA polymerase to move along the DNA and replicate the exact amount of genetic material needed for the daughter cell.
      Courtesy of PBS production "DNA: The Secret of Life"
      In the video above, imagine that the DNA being replicated was wrapped "just right" around the histones and that the video has zoomed in on a strand of DNA between two histones that is now being replicated. This "just right" wrapping allows DNA polymerase and all other proteins involved with DNA Replication to successfully duplicate the double-stranded DNA. The purple proteins are the DNA Polymerases and the dark blue protein that is splitting the two strands from each other is helicase.
  2. When too many histones are produced, DNA Replication and Cell Division are inhibited, resulting in cell death.

Histone Replication Mirors DNA Replication

With the second observation, it is important to note that histone replication mirrors DNA replication. Just as newly divided cells need copies of DNA, they also need copies of all cellular components and proteins in order to continue to survive and divide. In order to create copies, the cell needs instructions to make organelles, proteins, and membranes. Imagine that DNA is the recipe book for all components that the cell needs to replicate. If the recipe for a particular protein, for example, is missing or gets changed, the resulting product may be changed. Additionally, if the cell does not know when to stop making the protein "recipe", it will continue to produce that organelle or protein.

Histones are one of the specific proteins for which DNA contains the recipe. Under normal circumstances, the cell knows when to make histones, how to make them, and when to stop making histones. If the instructions for making histones are not turned off at the end of S phase, the cell will continue to make histones, resulting in many more than necessary. Having too many histones wrapped with DNA causes the DNA to become much more compact than necessary. As we said in the first observation, if there is "too much" wrapping of DNA around histones (e.g. more compaction of DNA than usual), DNA replication cannot occur. Therefore, cells containing the mutant command protein gene get overwhelmed by the compaction caused by the huge amount of histones in the cell, stop dividing, and eventually die.

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