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Are nucleoside triphosphates (NTPs) actively delivered to RNA polymerase (similarly dNTPs to DNA polymerase) through some active chaperoned process, or are they so abundant in the nucleus that they rely simply on stochastic diffusion?

Are there any relevant papers on this process?

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    $\begingroup$ You or someone else seems to have changed the question from dNTPs and DNA polymerase to NTPs and RNA polymerase. This negates the answer that @BlueFoxy went to the trouble of providing. In any case I'm still not clear what you are asking. Are you asking about how the precursors get from the cytoplasm, where they are thought to be synthesized, to the nucleus, or to the polymerase when already in the nucleus? If the later, why do you think the situation is any different from any other stochastic process involving enzymes and substrates? $\endgroup$ – David Aug 30 '16 at 10:21
  • $\begingroup$ The principles would be the same for NTP-RNAP and dNTP-DNAP so it doesn't really matter. $\endgroup$ – WYSIWYG Aug 30 '16 at 10:57
  • $\begingroup$ @WYSIWYG — Not necessarily, although the whole idea of chaperones for (d)NTPs seems absurd to me. I've changed the title slightly as I see the question has been edited to include this. $\endgroup$ – David Aug 30 '16 at 12:23
  • $\begingroup$ There have been significant edits to my question by moderators or others, and I'm not sure I understand the wording of my own question anymore. My question is literally just the colloquial "is there something in the nucleus actively delivering nucleic bases to polymerase to attach to new DNA strands, or does it just happen through random collisions/diffusion) $\endgroup$ – Mike Flynn Aug 30 '16 at 12:35
  • $\begingroup$ @MikeFlynn We just made the statement more scientifically accurate. Don't worry; we have not changed the meaning. If left to what it was, your question would have been considered unclear. $\endgroup$ – WYSIWYG Aug 30 '16 at 13:24
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The amount of dNTPs is so important and sensitive the level of dNTPs should be optimum not lower or higher. Lower amounts lead to insufficiency and higher amounts lead to increased mutation rates. Also, this optimum amount of dNTPs should last for a couple of minutes to supply dNTPs needed for replication. The delivery of dNTPs is due to molecular signalling & stochastic diffusion.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847218/

"Eukaryotic cells contain a delicate balance of minute amounts of the four deoxyribonucleoside triphosphates (dNTPs), sufficient only for a few minutes of DNA replication. Both a deficiency and a surplus of a single dNTP may result in increased mutation rates"


http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2010.01719.x/pdf

"Optimization of intracellular concentrations of dNTPs is critical for the fidelity of DNA synthesis during DNA replication and repair because levels that are too high or too low can easily lead to increased rates of mutagenesis"


http://www.nature.com/ncb/journal/v14/n7/full/ncb2540.html

"Production of deoxyribonucleotide triphosphates (dNTPs) is essential for DNA synthesis during replication and repair, and abnormal or imbalanced dNTP levels increases mutation frequency. Pagano and colleagues now demonstrate that the SCF-cyclin F ubiquitin ligase controls dNTP production during the cell cycle and following genotoxic stress"


http://www.ncbi.nlm.nih.gov/pubmed/22234185

"alterations in dNTP pools are associated with increased mutagenesis, genomic instability and tumourigenesis"


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  • $\begingroup$ To be clear, are you saying that nucleosides can arrive both by chaperones and diffusion? $\endgroup$ – James Aug 30 '16 at 7:15
  • $\begingroup$ @James chaperons have nothing to do with dNTPs delivery at least not directly . faculty.washington.edu/baneyx/Chaperones/Chaperones.html chaperons just control the folding and unfolding process of proteins by interacting with mediators . $\endgroup$ – BlueFoxy Aug 30 '16 at 11:01
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    $\begingroup$ You provide some good references on the regulation of dNTP synthesis, but you do NOT answer the question. I would up-vote your answer if you added a conclusion on the lines of "In none of these papers is there any suggestion that the dNTPs enter the nucleus and reach the DNA polymerase by any other mechanism than diffusion. Furthermore, with rare exceptions (e.g. exotic metal cofactors), chaperones are only involved in the delivery of proteins. In the absence of any published evidence it is reasonable to conclude chaperones are not involved." $\endgroup$ – David Aug 30 '16 at 12:20
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Many processes in the cell, also processes involving compounds that have a lower abundance than the NTPs, rely on stochastic diffusion. Even the polymerase is not actively transported to the nucleic acid, it just diffuses until it finds a proper binding place.

Also, the energetics of active transport would not make sense. One of the NTPs is ATP, one of the major energy carriers in the cell. It would make little sense for the cell to actively transport ATP to the polymerase on the nucleic acid, because active transport needs energy, thus likely ATP or something similar itself. This would then have to diffuse to the transporter to keep it moving. It would be cheaper for the cell to just use that ATP directly, because you're relying on diffusion in both cases.

This is not even taking into account that 1 protein cannot actively move across the cell, even expending energy. Systems that do something like this are much more complex, such as myosin (moving along actin filaments).

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  • $\begingroup$ One of the dNTPs is certainly NOT ATP, it is dATP. And chaperones do not necessarily require energy. I'm afraid it's your arguments that don't make sense, irrespective of the validity of your conclusion. $\endgroup$ – David Aug 30 '16 at 7:59
  • $\begingroup$ Chaperones aren't diffusing any faster without energy, and sorry for automatically typing dNTPs (although you could have just corrected this). $\endgroup$ – VonBeche Aug 30 '16 at 8:21
  • $\begingroup$ As regards dNTP and NTP, I think the question has been changed from one originally about DNA and I didn't notice. I assume we are talking of chaperone proteins. I know of no chaperone proteins (or indeed any other protein) which uses the energy from hydrolysis of ATP to increase its diffusion in solution (rather than across a membrane, which is not relevant to the question). Do you? And what do you mean by 'active transport' needing energy? Are you thinking about active cation transport, which is irrelevant here? $\endgroup$ – David Aug 30 '16 at 10:07
  • $\begingroup$ Diffusion is free, if you want to actively create a concentration gradient (higher at one point than another) it's going to cost energy, no matter how you do it. $\endgroup$ – VonBeche Aug 30 '16 at 11:09
  • $\begingroup$ I know diffusion is free, but you seemed to be suggesting you could use "energy" to accelerate it. But who wants to create a concentration gradient? If the NTPs diffuse to the polymerase they will be removed by reaction, pulling more into the nucleus by mass action. $\endgroup$ – David Aug 30 '16 at 11:18

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