Polymerase

{{Short description|Class of enzymes which synthesize nucleic acid chains or polymers}} [[Image:Taq polimerase.png|thumb|Ribbon diagram representation of Taq DNA polymerase]]

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 half ladder replication.

A DNA polymerase from the thermophilic bacterium, ''Thermus aquaticus'' (''Taq'') (PDB [http://www.rcsb.org/pdb/cgi/explore.cgi?pid=288631034363198&pdbId=1BGX 1BGX] {{Webarchive|url=https://web.archive.org/web/20070704130909/http://www.rcsb.org/pdb/cgi/explore.cgi?pid=288631034363198&pdbId=1BGX |date=2007-07-04 }}, 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 is also known to have template independent and template dependent activities.

== By function == {| class="wikitable floatright" |+ Classes of Template dependent polymerase ! !Produces DNA !Produces RNA |- !Template is DNA |DNA-dependent DNA polymerase (DdDp)<br/> or common DNA polymerases |DNA-dependent RNA polymerase (DdRp)<br/> or common RNA polymerases |- !Template is RNA |RNA-dependent DNA polymerase (RdDp)<br/> or Reverse transcriptase (RT) |RNA-dependent RNA polymerase (RdRp)<br/> 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.<ref>{{cite journal | vauthors = Loc'h J, Rosario S, Delarue M | title = Structural Basis for a New Templated Activity by Terminal Deoxynucleotidyl Transferase: Implications for V(D)J Recombination | journal = Structure | volume = 24 | issue = 9 | pages = 1452–63 | date = September 2016 | pmid = 27499438 | doi = 10.1016/j.str.2016.06.014 | doi-access = free }}</ref> **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 {{clear|right}}

== 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.<ref name="pmid9309225">{{cite journal | vauthors = Hansen JL, Long AM, Schultz SC | title = Structure of the RNA-dependent RNA polymerase of poliovirus | journal = Structure | volume = 5 | issue = 8 | pages = 1109–22 | date = August 1997 | pmid = 9309225 | doi = 10.1016/S0969-2126(97)00261-X | doi-access = free }}</ref> The latter is seen in all multi-subunit RNA polymerases, in cRdRP, and in "family D" DNA polymerases found in archaea.<ref name="pmid11839495">{{cite journal | vauthors = Cramer P | title = Multisubunit RNA polymerases | journal = Current Opinion in Structural Biology | volume = 12 | issue = 1 | pages = 89–97 | date = February 2002 | pmid = 11839495 | doi = 10.1016/S0959-440X(02)00294-4 }}</ref><ref name=qde1-mono>{{cite journal | vauthors = Sauguet L | title = The Extended "Two-Barrel" Polymerases Superfamily: Structure, Function and Evolution | journal = Journal of Molecular Biology | volume = 431 | issue = 20 | pages = 4167–4183 | date = September 2019 | pmid = 31103775 | doi = 10.1016/j.jmb.2019.05.017 | doi-access = free }}</ref> The "X" family represented by DNA polymerase beta has only a vague "palm" shape, and is sometimes considered a different superfamily ({{InterPro|IPR043519}}).<ref>{{cite journal | vauthors = Salgado PS, Koivunen MR, Makeyev EV, Bamford DH, Stuart DI, Grimes JM | title = The structure of an RNAi polymerase links RNA silencing and transcription | journal = PLOS Biology | volume = 4 | issue = 12 | pages = e434 | date = December 2006 | pmid = 17147473 | pmc=1750930 | doi = 10.1371/journal.pbio.0040434 | doi-access = free }}</ref>

Primases generally don't fall into either category. Bacterial primases usually have the Toprim domain, and are related to topoisomerases and mitochondrial helicase twinkle.<ref>{{cite journal | vauthors = Aravind L, Leipe DD, Koonin EV | title = Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins | journal = Nucleic Acids Research | volume = 26 | issue = 18 | pages = 4205–13 | date = September 1998 | pmid = 9722641 | pmc = 147817 | doi = 10.1093/nar/26.18.4205 }}</ref> 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.<ref>{{cite journal | vauthors = Iyer LM, Koonin EV, Leipe DD, Aravind L | title = Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: structural insights and new members | journal = Nucleic Acids Research | volume = 33 | issue = 12 | pages = 3875–96 | date = 2005 | pmid = 16027112 | pmc = 1176014 | doi = 10.1093/nar/gki702 }}</ref>

<gallery> File:WikiHandDNAPolII.png|Right hand structure of Bacteriophage RB69, a family B DdRP.    </gallery>

== Modification of activity == Scientists have modified the activity of nucleic acid polymerases in many ways, from rational design to directed evolution, to achieve changes from incremental tweaks like higher speed/accuracy/thermostability or major shifts such as conversion of template and product types.

=== Nucleic acid types === All known natural reverse transcriptases evovled from an ancestor that has no proofreading ability, causing a low fidelity. In 2016, scientists successfully used directed evolution to modify the proofreading ''Thermococcus kodakarensis'' DNA-directed DNA polymerase into what they call a ''reverse transcribing xenotranscriptase'' (RTX). This new enzyme is able to copy from and proofread with RNA ''and'' DNA templates. It is expected to improve the accuracy in RNA sequencing and other forms of RT-PCR.<ref>{{cite journal |last1=Ellefson |first1=JW |last2=Gollihar |first2=J |last3=Shroff |first3=R |last4=Shivram |first4=H |last5=Iyer |first5=VR |last6=Ellington |first6=AD |title=Synthetic evolutionary origin of a proofreading reverse transcriptase. |journal=Science |date=24 June 2016 |volume=352 |issue=6293 |pages=1590–3 |doi=10.1126/science.aaf5409 |pmid=27339990 |bibcode=2016Sci...352.1590E }}</ref> It was commercialized some time before April 2018.<ref>{{cite web |title=WarmStart® RTx Reverse Transcriptase |url=https://www.neb.com/en/products/m0380-warmstart-rtx-reverse-transcriptase |website=www.neb.com}}</ref>

In 2022, selective mutagenesis converted a ''Kod'' DNA polymerase into one that produces α-l-threofuranosyl nucleic acid or threose nucleic acid (TNA).<ref>{{cite journal |last1=Nikoomanzar |first1=A |last2=Vallejo |first2=D |last3=Yik |first3=EJ |last4=Chaput |first4=JC |title=Programmed Allelic Mutagenesis of a DNA Polymerase with Single Amino Acid Resolution. |journal=ACS Synthetic Biology |date=17 July 2020 |volume=9 |issue=7 |pages=1873–1881 |doi=10.1021/acssynbio.0c00236 |pmid=32531152}}</ref> This result has been improved in 2024 and 2025 using HR-accelerated directed evolution, yielding several enzymes with near-natural speed and fidelity.<ref>{{cite journal |last1=Hajjar |first1=Mohammad |last2=Maola |first2=Victoria A. |last3=Lee |first3=Joy J. |last4=Holguin |first4=Manuel J. |last5=Quijano |first5=Riley N. |last6=Nguyen |first6=Kalvin K. |last7=Ho |first7=Katherine L. |last8=Medina |first8=Jenny V. |last9=Botello-Cornejo |first9=Elionel |last10=Barpuzary |first10=Bhawna |last11=Chim |first11=Nicholas |last12=Chaput |first12=John C. |title=Directed evolution of a TNA polymerase identifies independent paths to fidelity and catalysis |journal=Nature Communications |date=19 December 2025 |volume=17 |issue=1 |article-number=925 |doi=10.1038/s41467-025-67652-1|doi-access=free |pmid=41413390 |pmc=12830623 }}</ref>

In 2025, scientists used directed evolution, accelerated by homologous recombination (HR), to change a DNA polymerase into an RNA polymerase. It is able to perform transcription quickly (3 nt/s) and accurately (>99%). It is also a somewhat "universal" polymerase, being also capable of RNA-directed DNA production (reverse transcription) and chimeric DNA–RNA amplification.<ref>{{cite journal |last1=Medina |first1=EL |last2=Maola |first2=VA |last3=Hajjar |first3=M |last4=Ko |first4=GK |last5=Ho |first5=EJ |last6=Horton |first6=AR |last7=Chim |first7=N |last8=Chaput |first8=JC |title=Rapid evolution of a highly efficient RNA polymerase by homologous recombination. |journal=Nature Chemical Biology |date=7 January 2026 |doi=10.1038/s41589-025-02124-7 |pmid=41501182}}</ref>

== References == {{Reflist}}

==External links==

Category:EC 2.7.7 Category:Enzymes