2020年2月10日 星期一

DNA Polymerases v. RNA Polymerases



The overall process of DNA replication requires the synthesis of DNA and RNA, thus involves both DNA polymerases and RNA polymerases.

Polymerases are enzymes that synthesize nucleic acids by forming phosphodiester (PDE) bonds.

Both types of polymerases attach to the DNA template strand, synthesizing nucleic acid strands in the 5’→3’ direction, and scanning the template strand in the 3’→5’ direction. As a result, the newly synthesized strand is complementary and antiparallel to the template strand.

DNA polymerases, however, require a primer, whereas RNA polymerases do not. That is, DNA polymerases cannot initiate strand synthesis like RNA polymerases do.

They also use different substrates. DNA polymerases use dNTP substrates whereas RNA polymerases use NTP substrates. Makes sense, right?

In addition, DNA polymerases are capable of correcting mistakes (“proofreading”) during the synthesis, whereas RNA polymerases cannot. This also makes sense. If you’ve studied gene expression, you would have known that a certain phenomenon known as “wobble” exists in tRNA, which results in flexible base pairing at the third nucleotide base of an mRNA codon (in this case, 3’-UCU-5’ can base-pair with either the mRNA codon 5’-AGA-3’ or 5’-AGG-3’, both of which codes for arginine). 

“Wobble” allows RNA to be less “accurate” compare with the original DNA template strand. DNA polymerases, on the other hand, need to maintain high fidelity of its gene information, utilizing enzymes called nucleases to hydrolyze PDE bonds and remove mispaired nucleotides, in this case, the 3’→5’ Exonuclease (exonucleases remove nucleotides from either the 5’ or the 3’ end of a nucleic acid, while endonucleases cut within the nucleic acid and release nucleic acid fragments).



Comparison of DNA and RNA Polymerases

In prokaryotes, DNA polymerase III synthesizes DNA in the 5'→3' direction of both the leading and the lagging strand. In the lagging strand, DNA polymerase I is responsible for removing the RNA primer and filling the resulting gap.

In eukaryotes, things are far more complicated. 

  • DNA polymerase δ synthesizes the leading strand during replication. 
  • DNA polymerase α synthesizes the lagging strand during replication.
  • DNA polymerase γ replicates mitochondrial DNA.
  • DNA polymerase β and ε are thought to participate primarily in DNA repair. DNA polymerase ε may substitute for DNA polymerase δ in certain cases.


Reference:

Lynne B. Jorde. 2002. USMLE Step 1: Biochemistry Notes.

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