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Pathway · 5 proteins

DNA synthesis

Polymerase, clamp and loader subunits support processive replication.

How it works

  1. DNA polymerase III alpha is the catalytic subunit. The beta subunit is the sliding clamp that keeps the polymerase on the template, and the delta subunit is part of the clamp loader.
  2. The gamma/tau subunits belong to the same clamp-loader complex and couple ATP hydrolysis to opening and closing the clamp, which is what makes synthesis processive rather than distributive.
  3. VF5 lists further DNA polymerase III subunits as well, so the replicative apparatus is assembled from separate proteins rather than a single polypeptide.

Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.

Its proteins

ProteinECReaction (UniProt)Metal or clusterAmino acidsCertainty
DNA polymerase III subunit alpha2.7.7.7DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate—1161Step named
Probable DNA polymerase III subunit delta2.7.7.7DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate—350Step named
AAA+ ATPase domain-containing protein———305Step named
DNA polymerase III subunit gamma/tau2.7.7.7DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate—473Step named
Beta sliding clamp———363Step named

Origins

How could DNA be copied before DNA polymerase and its helpers existed?

How it was discovered

  1. 1956Arthur Kornberg discovers DNA polymerase, the enzyme that builds new DNA on a template.Kornberg et al., Biochimica et Biophysica Acta 21:197–198 (1956)
Naturalistic proposal

Enzymes that copy RNA, found in RNA viruses, are cited as having implications for self-replicating molecules that may have existed before cells.

Design analysis

Copying DNA takes an ensemble: a helicase to open the helix, single-strand binding proteins, a primase to start each strand, polymerases, a proofreading exonuclease, a ligase to seal the pieces and gyrase to relieve the twisting. Five proteins in this pathway alone are needed to build new strands.

From the books: Nelson & Cox, Lehninger Principles of Biochemistry, p. 1050; Rana, The Cell's Design, ch. 11.

The wider question for this part of the cell: origins for copying and repairing the genome.

Sources

Other pathways in this group: DNA damage repair · Topology management · Joining and end processing · Recombination and restart · Chromosome preparation · Initiation and opening · Homologous recombination · Base excision repair · Cysteine and methionine metabolism · Not yet placed in a pathway