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enter image description here

Hi there,

I am confused about how the nucleophilic attack occurs in DNA replication.I watched this video from a biology professor (https://www.youtube.com/watch?v=y4hKibS2fAo)

I watched this video which stated that during DNA replication, the hydroxl group forms a covalent bond with the phosphate and the two phosphorus groups are a leaving group.

I understand the basics of these kinds of reactions, but this one just seems confusing. I can see that the oxygen which was part of the hydroxl group forms a covalent bond with phosphorus. But what happens to the hydrogen? And why does the the double bond and position of the HO change position from the first picture to the second picture?

There are also some pictures which show water being produced. But the video states that the hydroxl group is forming a bond with the phosphate group. How does that work?

Thanks a lot

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Polymerases uses a two-metal ion mechanism to carry out the addition of a new NTP to a growing RNA strand. Two Mg2+ ions are used in this process; metal ion A is involved in the formation of the nucleophile (O-) for the SN2 reaction to occur and metal ion B is involved in the stabilization of the transition state in the reaction. For the addition of a NTP to a RNA strand to occur, an activated 3’ hydroxyl group (O-) acts a nucleophile and attacks the alpha phosphate of the incoming NTP. The reaction is initiated by a deprotonation event. Metal ion A aids with this deprotonation as it reduces the pKa of the hydroxyl (so it is more acidic), making it easier to deprotonate and form the nucleophile, the proton is accepted by a nearby aspartate residue (not water) - doi: 10.1021/ja403842j. After the hydroxyl attack, the mechanism proceeds through a pentacovalent transition state like in a standard Sn2 reaction and the pyrophosphate group (PPi) is kicked out. The image is not mine but comes from this paper: https://doi.org/10.1038/34542, which is quite good, as is this paper: doi: 10.1074/jbc.274.25.17395 and this one https://doi.org/10.1016/j.molcel.2006.03.013 enter image description here

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  • $\begingroup$ Perhaps you could properly cite the references you are using in case the links become broken in future. $\endgroup$ – canadianer Sep 10 at 20:55
  • $\begingroup$ I have included the doi's instead, hopefully this is better $\endgroup$ – pepsiandsoda Sep 10 at 21:18

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