Polymerase

Class of enzymes which synthesize nucleic acid chains or polymers

In biochemistry, a polymerase is an enzyme (EC 2.7.7.6/7/19/48/49) that synthesizes long chains of polymers or nucleic acids. DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base-pairing interactions or RNA by half ladder replication.

A DNA polymerase from the thermophilic bacterium, Thermus aquaticus (Taq) (PDB 1BGX, EC 2.7.7.7) is used in the polymerase chain reaction, an important technique of molecular biology.

A polymerase may be template-dependent or template-independent. Poly-A-polymerase is an example of template independent polymerase. Terminal deoxynucleotidyl transferase also known to have template independent and template dependent activities.

Types

By function

Classes of Template dependent polymerase
	DNA-polymerase	RNA-polymerase
Template is DNA	DNA dependent DNA-polymerase or common DNA polymerases	DNA dependent RNA-polymerase or common RNA polymerases
Template is RNA	RNA dependent DNA polymerase or Reverse transcriptase	RNA dependent RNA polymerase or RdRp or RNA-replicase

DNA polymerase (DNA-directed DNA polymerase, DdDP)
- Family A: DNA polymerase I; Pol γ, θ, ν
- Family B: DNA polymerase II; Pol α, δ, ε, ζ
- Family C: DNA polymerase III holoenzyme
- Family X: Pol β, λ, μ
  - Terminal deoxynucleotidyl transferase (TDT), which lends diversity to antibody heavy chains.^[1]
- Family Y: DNA polymerase IV (DinB) and DNA polymerase V (UmuD'2C) - SOS repair polymerases; Pol η, ι, κ
Reverse transcriptase (RT; RNA-directed DNA polymerase; RdDP)
- Telomerase
DNA-directed RNA polymerase (DdRP, RNAP)
- Multi-subunit (msDdRP): RNA polymerase I, RNA polymerase II, RNA polymerase III
- Single-subunit (ssDdRP): T7 RNA polymerase, POLRMT
- Primase, PrimPol
RNA replicase (RNA-directed RNA polymerase, RdRP)
- Viral (single-subunit)
- Eukaryotic cellular (cRdRP; dual-subunit)
Template-less RNA elongation
- Polyadenylation: PAP, PNPase

By structure

Polymerases are generally split into two superfamilies, the "right hand" fold (InterPro: IPR043502) and the "double psi beta barrel" (often simply "double-barrel") fold. The former is seen in almost all DNA polymerases and almost all viral single-subunit polymerases; they are marked by a conserved "palm" domain.^[2] The latter is seen in all multi-subunit RNA polymerases, in cRdRP, and in "family D" DNA polymerases found in archaea.^[3]^[4] The "X" family represented by DNA polymerase beta has only a vague "palm" shape, and is sometimes considered a different superfamily (InterPro: IPR043519).^[5]

Primases generally don't fall into either category. Bacterial primases usually have the Toprim domain, and are related to topoisomerases and mitochondrial helicase twinkle.^[6] Archae and eukaryotic primases form an unrelated AEP family, possibly related to the polymerase palm. Both families nevertheless associate to the same set of helicases.^[7]

Right hand structure of Bacteriophage RB69, a family B DdRP.

References

^ Loc'h J, Rosario S, Delarue M (September 2016). "Structural Basis for a New Templated Activity by Terminal Deoxynucleotidyl Transferase: Implications for V(D)J Recombination". Structure. 24 (9): 1452–63. doi:10.1016/j.str.2016.06.014. PMID 27499438.
^ Hansen JL, Long AM, Schultz SC (August 1997). "Structure of the RNA-dependent RNA polymerase of poliovirus". Structure. 5 (8): 1109–22. doi:10.1016/S0969-2126(97)00261-X. PMID 9309225.
^ Cramer P (February 2002). "Multisubunit RNA polymerases". Current Opinion in Structural Biology. 12 (1): 89–97. doi:10.1016/S0959-440X(02)00294-4. PMID 11839495.
^ Sauguet L (September 2019). "The Extended "Two-Barrel" Polymerases Superfamily: Structure, Function and Evolution". Journal of Molecular Biology. 431 (20): 4167–4183. doi:10.1016/j.jmb.2019.05.017. PMID 31103775.
^ Salgado PS, Koivunen MR, Makeyev EV, Bamford DH, Stuart DI, Grimes JM (December 2006). "The structure of an RNAi polymerase links RNA silencing and transcription". PLoS Biology. 4 (12): e434. doi:10.1371/journal.pbio.0040434. PMC 1750930. PMID 17147473.
^ Aravind L, Leipe DD, Koonin EV (September 1998). "Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins". Nucleic Acids Research. 26 (18): 4205–13. doi:10.1093/nar/26.18.4205. PMC 147817. PMID 9722641.
^ Iyer LM, Koonin EV, Leipe DD, Aravind L (2005). "Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: structural insights and new members". Nucleic Acids Research. 33 (12): 3875–96. doi:10.1093/nar/gki702. PMC 1176014. PMID 16027112.

External links

DNA replication (comparing prokaryotic to eukaryotic)

Initiation

Prokaryotic (initiation)	Pre-replication complex dnaC Helicase dnaA dnaB T7 Primase dnaG
Eukaryotic (preparation in G1 phase)	Pre-replication complex Origin recognition complex ORC1 ORC2 ORC3 ORC4 ORC5 ORC6 Cdc6 Cdt1 Minichromosome maintenance MCM2 MCM3 MCM4 MCM5 MCM6 MCM7 Licensing factor Autonomously replicating sequence Single-strand binding protein SSBP2 SSBP3 SSBP4 RNase H RNASEH1 RNASEH2A Helicase: HFM1 Primase: PRIM1 PRIM2
Both	Origin of replication/Ori/Replicon Replication fork Lagging and leading strands Okazaki fragments Primer

Replication

Prokaryotic (elongation)	DNA polymerase III holoenzyme dnaC dnaE dnaH dnaN dnaQ dnaT dnaX holA holB holC holD holE Replisome DNA ligase DNA clamp Topoisomerase DNA gyrase Prokaryotic DNA polymerase: DNA polymerase I Klenow fragment
Eukaryotic (synthesis in S phase)	Replication factor C RFC1 Flap endonuclease FEN1 Topoisomerase Replication protein A RPA1 Eukaryotic DNA polymerase: alpha POLA1 POLA2 PRIM1 PRIM2 delta POLD1 POLD2 POLD3 POLD4 epsilon POLE POLE2 POLE3 POLE4 DNA clamp PCNA Control of chromosome duplication
Both	Movement: Processivity DNA ligase

Termination

Telomere: Telomerase
- TERT
- TERC
- DKC1

Transferases: phosphorus-containing groups (EC 2.7)

2.7.1-2.7.4:
phosphotransferase/kinase
(PO₄)

2.7.1: OH acceptor	Hexo- Gluco- Fructo- Hepatic Galacto- Phosphofructo- 1 Liver Muscle Platelet 2 Riboflavin Shikimate Thymidine ADP-thymidine NAD⁺ Glycerol Pantothenate Mevalonate Pyruvate Deoxycytidine PFP Diacylglycerol Phosphoinositide 3 Class I PI 3 Class II PI 3 Sphingosine Glucose-1,6-bisphosphate synthase
2.7.2: COOH acceptor	Phosphoglycerate Aspartate kinase
2.7.3: N acceptor	Creatine
2.7.4: PO₄ acceptor	Phosphomevalonate Adenylate Nucleoside-diphosphate Uridylate Guanylate Thiamine-diphosphate

2.7.6: diphosphotransferase
(P₂O₇)

2.7.7: nucleotidyltransferase
(PO₄-nucleoside)

Polymerase

DNA polymerase	DNA-directed DNA polymerase I/A γ θ ν T7 Taq II/B α δ ε ζ Pfu III/C IV/X β λ μ TDT V/Y η ι κ RNA-directed DNA polymerase Reverse transcriptase Telomerase
RNA polymerase	Template-directed RNA polymerase I II III IV V ssRNAP POLRMT Primase 1 2 PrimPol RNA-dependent RNA polymerase Polyadenylation PAP PNPase

Phosphorolytic
3' to 5' exoribonuclease

Nucleotidyltransferase

Guanylyltransferase

mRNA capping enzyme

Other

2.7.8: miscellaneous

Phosphatidyltransferases	CDP-diacylglycerol—glycerol-3-phosphate 3-phosphatidyltransferase CDP-diacylglycerol—serine O-phosphatidyltransferase CDP-diacylglycerol—inositol 3-phosphatidyltransferase CDP-diacylglycerol—choline O-phosphatidyltransferase
Glycosyl-1-phosphotransferase	N-acetylglucosamine-1-phosphate transferase

2.7.10-2.7.13: protein kinase
(PO₄; protein acceptor)

2.7.10: protein-tyrosine	see tyrosine kinases
2.7.11: protein-serine/threonine	see serine/threonine-specific protein kinases
2.7.12: protein-dual-specificity	see serine/threonine-specific protein kinases
2.7.13: protein-histidine	Protein-histidine pros-kinase Protein-histidine tele-kinase Histidine kinase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)