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The overall chemical reaction catalyzed by both DNA polymerases is Poly(nucleotide)n-3'OH + dNTP Poly(nucleotide)n+1 -3'-OH + PPi The total free energy change is + 0.5 kcal/mol. How does polymerization occur in vivo?

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Polymerization of DNA occurs in vivo through a process called DNA replication. It involves the coordinated action of DNA polymerase enzymes, which catalyze the synthesis of new DNA strands using existing DNA templates and deoxyribonucleotide triphosphates (dNTPs).

The overall chemical reaction you mentioned represents the addition of a deoxyribonucleotide (dNTP) to the growing DNA strand. The reaction involves the transfer of a dNTP molecule to the 3'-OH group of the existing DNA chain, resulting in the formation of a phosphodiester bond between the incoming dNTP and the last nucleotide of the growing DNA strand. This process releases inorganic pyrophosphate (PPi).

The overall free energy change for the reaction is +0.5 kcal/mol, indicating a slightly endergonic process. However, in vivo, DNA polymerization is made energetically favorable by coupling it with the hydrolysis of pyrophosphate to inorganic phosphate (Pi). Pyrophosphate hydrolysis is an exergonic reaction, meaning it releases energy. The high concentration of inorganic phosphate in the cell helps drive the overall reaction forward, pulling it towards completion.

Furthermore, DNA polymerases play a crucial role in the polymerization process. They not only catalyze the addition of nucleotides but also possess proofreading and editing functions to ensure the accuracy of DNA replication. DNA polymerases have exonuclease activity, allowing them to remove mismatched or damaged nucleotides from the growing DNA strand, replacing them with the correct ones.

Overall, in vivo DNA polymerization occurs by the sequential addition of dNTPs to the growing DNA strand, catalyzed by DNA polymerase enzymes. The energy required for the endergonic polymerization reaction is provided by the exergonic hydrolysis of pyrophosphate, and the accuracy of the process is maintained through proofreading mechanisms of DNA polymerases.
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