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<StructureSection load='' size='350' side='right' scene='44/440019/Cv/2' caption='Family A DNA polymerase I complex with octylglucoside [[1taq]]'>
<StructureSection load='' size='350' side='right' scene='44/440019/Cv/2' caption='Family A DNA polymerase I complex with octylglucoside [[1taq]]'>


[[DNA polymerase]] '''(Dpo)''' reads a [[DNA|DNA strand]] and catalyzes the synthesis of its complementary strand. Dpo's are divided into 7 families according to their sequence homology and 3D structure similarities.<ref>PMID:10364165</ref> The families are:<br />
==Overview==
* Family A - replicative or repair Dpo.<br />
'''DNA polymerases''' are enzymes that play a key role in [[DNA]] replication. '''DNA replication''' is the process of splitting an existing double-stranded DNA molecule into two single strands of DNA, then using DNA polymerases to translate the single strands. The process of translation results in the creation of the '''complementary''' DNA strands and results in the creation of two double-stranded DNA molecules that are exact replicas of the original DNA molecule. The complementary strands are created in the 5'-3' direction. Certain DNA polymerases are also responsible for proofreading the newly synthesized DNA strand and using exonuclease to remove and replace any errors that occurred. DNA polymerases are divided into 7 families according to their sequence homology and 3D structure similarities.<ref>PMID:10364165</ref> The families are:
* Family B - replicative Dpo involved in processing DNA replication during cell division (includes eukaryotic Dpo α,δ,ε).<br />
* Family A - DNA replication and repair (includes DNA Polymerase I, γ)
* Family C - major replicative Dpo in bacteria (includes Dpo II, III, IV).<br />
* Family B - DNA replication and repair (includes DNA Polymerase II, α, δ, ε)
* Family D - replicative.  Present in archaea.<br />
* Family C - DNA replication in prokaryotes (includes DNA Polymerase III)
* Family X - eukaryotic repair Dpo (includes Dpo β,λ,σ,μ and terminal deoxynucleotidyl transferase).<br />
* Family D - DNA replication in archaea
* Family Y - replicative of damaged DNA (includes eukaryotic η,ι,κ).<br />
* Family X - DNA repair in eukaryotes (includes DNA Polymerase β, λ, μ)
* Family RT - reverse transcriptase.  See [[Reverse transcriptase]].<br />
* Family Y - DNA replication of damaged DNA (includes DNA Polymerase IV, V, η, ι, κ)
* Family RT - reverse transcriptase (See [[Reverse transcriptase]].)
 
==Function==
DNA polymerases are essential enzymes for [[DNA Replication, Transcription and Translation|DNA Replication]].[https://www.youtube.com/watch?v=v8gH404a3Gg] Before DNA polymerases can perform its part in DNA replication, other enzymes must unwind and split the double helical structure of DNA and signal for the initiation of replication. Once [[DNA primase]] has placed a primer on the template DNA strand, DNA polymerases can attach. These enzymes use the template strand of DNA to synthesize a complementary strand of DNA using the DNA building blocks called nucleotides. The order of the nucleotides on the complementary strand is determined by the base-pairing rules: cytosine with guanine and adenine with thymine.
 
During DNA synthesis, the DNA polymerases move along the template DNA strand in a 3'-5' direction and adds nucleotides to the new DNA strand in a 5'-3' direction. This causes the elongation of the new strand in a 5'-3' direction. Note that the direction of the newly formed DNA strand is opposite of the template DNA strand. This makes the resulting double-stranded DNA molecule complementary and '''anti-parallel'''.
 
DNA polymerases are some of the most accurate enzymes and have about one mistake for every one billion copies. When a mistake is made, many of the DNA polymerases have the ability to proofread the newly synthesized DNA and correct any mistakes made during replication. The enzymes proofread in the 5'-3' direction. When an error is found, the misplaced nucleotide is cut out so the correct nucleotide can be inserted. This process is often referred to as '''5'-3'exonuclease activity'''.
 
==Types of DNA Polymerase==
According to their sequence homology and 3D structure similarities, DNA Polymerases can be divided into 7 families: A, B, C, D, X, Y, and RT.<ref>PMID:10364165</ref>
 
{| class="wikitable"
|-
! Family
! Function
! Species
! Examples
|-
| A
| Replication and Repair
| Eukaryotes and Prokaryotes
| Pol I and Pol γ
|-
| B
| Replication and Repair
| Eukaryotes and Prokaryotes
| Pol II, Pol α, Pol δ, and Pol ε
|-
| C
| Replication
| Prokaryotes
| Pol III
|-
| D
| Replication
| Archaea
| Unknown
|-
| X
| Replication and Repair
| Eukaryotes
| Pol β, Pol μ, and Pol λ
|-
| Y
| Replication and Repair
| Eukaryotes and Prokaryotes
| Pol IV, Pol V, Pol η, Pol κ, and Pol ι
|-
| RT
| Replication and Repair
| Eukaryotes, Viruses, and Retrovirus
| Telomerase and Hepatitis B virus
|}
 
===Eukaryotic Polymerase===
 
====Polymerase γ====
Polymerase γ is considered a Family A polymerase. Pol γ's main function is to replicate and repair '''mitochondrial DNA (mtDNA)'''. Pol γ can perform proofreading 3'–5' exonuclease activity. Mutations that cause limited or non-functioning Pol γ has a significant effect on mtDNA and is a common cause of autosomal mitochondrial disorders.
 
====Polymerase α, Polymerase δ, and Polymerase ε====
Members of family B, Pol α, Pol δ, and Pol ε are the main polymerases involved in DNA replication. Pol α binds with primase to form a complex. Primase creates and places an RNA primer, allowing Pol α to start replication. Pol δ then takes over the synthesis of the lagging strand from Pol α. It is believed that Pol ε synthesizes the leading strand during replication, while Pol δ primarily replicates the lagging strand. However, there have been some cases where Pol δ has been found to replicate the lagging and leading strand. Pol δ and ε also possess 3'-5' exonuclease activity capabilities.
 
====Family X====
Family X polymerases consist of polymerases like Pol β, Pol μ, and Pol λ. Pol β's main function is short-patch base excision repair, a repair pathway used for repairing alkylated or oxidized bases. Pol λ and Pol μ are essential for rejoining DNA double-strand breaks due to hydrogen peroxide and ionizing radiation, respectively. For more details see [[DNA polymerase beta]].
 
====Polymerases η, Polymerase ι, and Polymerase κ====
Polymerase η, Polymerase ι, and Polymerase κ are Family Y DNA polymerases involved in the DNA repair by '''translesion synthesis'''. Polymerases in Family Y are prone to errors during DNA synthesis. Pol η is important for the accurate translesion synthesis of DNA damage resulting from ultraviolet radiation. The function of Pol κ is not completely understood, but it is thought to act as an extender or inserter of a specific base at certain DNA lesions. All three translesion synthesis polymerases are activated by stalled replicative DNA polymerases.
 
 
===Prokaryotic Polymerase===
 
====DNA Polymerase I====
[[DNA Polymerase I]] is a family A enzyme whose main function is excision repair of DNA strands through 3'-5' and 5'-3' exonuclease. This polymerase also helps with Okazaki fragment maturation. '''Okazaki fragments''' are short synthesized strands of DNA that form the lagging strand during DNA replication. When Polymerase I does replicate, it starts adding nucleotides at the RNA primer and moves in the 5'-3' direction. This polymerase is also the major polymerase in ''E. coli''. See also [[Taq DNA polymerase (Hebrew)]].
<scene name='44/440019/Cv/4'>Octylglucoside binding site</scene> in Family A DNA polymerase I ([[1taq]]).
 
<scene name='44/440019/Cv/5'>Zn coordination site contains 3 Asp residues</scene> in Family A DNA polymerase I ([[1taq]]).<ref>PMID:7637814</ref>
 
====DNA Polymerase II====
DNA polymerase II belongs to family B. It is responsible for 3'-5' exonuclease activity and restarting replication after the synthesis process has stopped due to damage in the DNA strand. Polymerase II is located at the replication fork in order to help direct the activity of other polymerases.   
 
 
====DNA Polymerase III====
DNA polymerase III is the primary enzyme involved in the replication of DNA. It belongs to family C and is responsible for synthesizing new DNA strands by adding nucleotides to the 3'-OH group of the primer. This enzyme also has 3'-5' exonuclease activity giving it the ability to check the synthesized DNA strand for errors.
 
For more details see [[Polymerase III homoenzyme beta subunit]] and [[Alpha Subunit of Thermus aquaticus DNA Polymerase III]].
====DNA Polymerase IV====
DNA polymerase IV is involved in '''non-targeted mutagenesis'''. Belonging to family Y, this enzyme is activated when synthesis at the replication fork stalls. once activated, Polymerase IV creates a checkpoint, stops replication, and allows time to properly repair lesions in the DNA strand. Polymerase IV is also involved in '''translesion synthesis''', a DNA repair mechanism. However, the enzyme lacks nuclease activity making it prone to errors in DNA replication
 
 
====DNA Polymerase V====
DNA polymerase V, in family Y, is highly regulated and only produced when DNA is damaged and requires translesion synthesis. Polymerase V, like polymerase IV, lacks all exonuclease function and is unable to proofread the synthesized DNA strand causing it to be less efficient.
 
===Reverse Transcriptase===
See [[Reverse transcriptase]].
 
 


Some Dpo terminology:<br />
Some Dpo terminology:<br />
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In the ''E. coli'', the EcDpo III subunits β, γ, δ, δ' are named '''clamp loader'''.  This complex assembles the β subunit sliding clamp unto the DNA.<br />
In the ''E. coli'', the EcDpo III subunits β, γ, δ, δ' are named '''clamp loader'''.  This complex assembles the β subunit sliding clamp unto the DNA.<br />


Prokaryotic DNA polymerases:<br />
* '''DNA polymerase I''': involved in excision repair.  Major polymerase in ''E. coli''.  For more details see [[DNA Polymerase I]].  See also [[Taq DNA polymerase (Hebrew)]].<br />
* '''DNA polymerase II''': active in replication forks.<br />
* '''DNA polymerase III''': involved in DNA replication.  For more details see [[Polymerase III homoenzyme beta subunit]] and [[Alpha Subunit of Thermus aquaticus DNA Polymerase III]].<br />
* '''DNA polymerase IV''': involved in non-targeted mutagenesis.<br />
* '''DNA polymerase V''': involved in translesion synthesis.<br />
Eukaryotic DNA polymerases:<br />
* '''Pol α,β,γ,δ,ε,ζ,η,ι,κ'''.  See also [[DNA polymerase beta]].<br />
* '''Rev1''' is a '''Dpo''' involved in replication over DNA lesions. <br />
* '''Terminal deoxynucleotidyl transferase (TdT)''' is a family X Dpo expressed in immature lymphoid cells.  TdT adds nucleotides to exons during antibody gene recombination.<br />
<scene name='44/440019/Cv/4'>Octylglucoside binding site</scene> in Family A DNA polymerase I ([[1taq]]).
<scene name='44/440019/Cv/5'>Zn coordination site contains 3 Asp residues</scene> in Family A DNA polymerase I ([[1taq]]).<ref>PMID:7637814</ref>
   
   
See also [[User:Karl E. Zahn/RB69 DNA polymerase (gp43)]]<br />
See also [[User:Karl E. Zahn/RB69 DNA polymerase (gp43)]]<br />
</StructureSection>
</StructureSection>
== 3D Structures of DNA polymerase ==  
== 3D Structures of DNA polymerase ==  
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
{{#tree:id=OrganizedByTopic|openlevels=0|
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**[[1qqc]] – DeDpo II – ''Desulfurococcus''<br />
**[[1qqc]] – DeDpo II – ''Desulfurococcus''<br />


*DNA polymerase III subunit alpha
*DNA polymerase III subunit α


**[[2hnh]], [[2hqa]] - EcDpo III subunit α catalytic fragment<br />
**[[2hnh]], [[2hqa]] - EcDpo III subunit α catalytic fragment<br />
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**[[1ok7]] - EcDpo III residues 1-366 + EcDpo IV C-terminal<br />
**[[1ok7]] - EcDpo III residues 1-366 + EcDpo IV C-terminal<br />


*DNA polymerase III subunit beta
*DNA polymerase III subunit β


**[[mmi]], [[2pol]], [[4k3s]], [[4pnv]], [[4pnw]] - EcDpo III subunit β<br />
**[[mmi]], [[2pol]], [[4k3s]], [[4pnv]], [[4pnw]] - EcDpo III subunit β<br />
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**[[4tsz]] - PaPol III β subunit + peptide<br />
**[[4tsz]] - PaPol III β subunit + peptide<br />


*DNA polymerase III subunit gamma
*DNA polymerase III subunit γ


**[[1njf]], [[1njg]] - EcDpo III subunit γ  N-terminal domains 1-2<br />
**[[1njf]], [[1njg]] - EcDpo III subunit γ  N-terminal domains 1-2<br />
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**[[1xxi]] - EcDpo III subunit γ,δ,δ’ + nucleotide<br />
**[[1xxi]] - EcDpo III subunit γ,δ,δ’ + nucleotide<br />


*DNA polymerase III subunit delta
*DNA polymerase III subunit δ


**[[1jqj]], [[1jql]] - EcDpo III subunit β,δ (mutant) <br />
**[[1jqj]], [[1jql]] - EcDpo III subunit β,δ (mutant) <br />
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**[[3glg]] - EcDpo III subunit δ,δ’,τ (mutant) + DNA<br />
**[[3glg]] - EcDpo III subunit δ,δ’,τ (mutant) + DNA<br />


*DNA polymerase III subunit epsilon
*DNA polymerase III subunit ε


**[[2gui]] – EcDpo III subunit ε N-terminal<br />
**[[2gui]] – EcDpo III subunit ε N-terminal<br />
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**[[2xy8]] - EcDpo III subunit ε,θ<br />
**[[2xy8]] - EcDpo III subunit ε,θ<br />


*DNA polymerase III subunit tau
*DNA polymerase III subunit τ


**[[2aya]] - EcDpo III subunit τ <br />
**[[2aya]] - EcDpo III subunit τ <br />
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**[[3gli]] - EcDpo III subunit δ,δ’,τ,ξ + DNA<br />
**[[3gli]] - EcDpo III subunit δ,δ’,τ,ξ + DNA<br />


*DNA polymerase III subunit theta
*DNA polymerase III subunit θ


**[[2xy8]] - EcDpo III subunit ε,θ<br />
**[[2xy8]] - EcDpo III subunit ε,θ<br />
**[[2axd]], [[2ae9]], [[1du2]] - EcDpo III subunit θ - NMR<br />
**[[2axd]], [[2ae9]], [[1du2]] - EcDpo III subunit θ - NMR<br />


*DNA polymerase III subunit chi
*DNA polymerase III subunit χ


**[[1em8]] - EcDpo III subunit ϕ,χ<br />
**[[1em8]] - EcDpo III subunit ϕ,χ<br />
**[[3sxu]] - EcDpo III subunit ϕ,χ + peptide<br />
**[[3sxu]] - EcDpo III subunit ϕ,χ + peptide<br />


*DNA polymerase III subunit phi
*DNA polymerase III subunit φ


**[[1em8]] - EcDpo III subunit ϕ,χ<br />
**[[1em8]] - EcDpo III subunit ϕ,χ<br />
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**[[1d5a]] – DeDpo <br />
**[[1d5a]] – DeDpo <br />


*DNA polymerase alpha
*DNA polymerase α


**[[4e2i]] – hDpo α subunit β + large T antigen – human<br />
**[[4e2i]] – hDpo α subunit β + large T antigen – human<br />
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**[[1n5g]], [[1k0p]], [[1k18]] - hDpo α zinc finger domain – NMR<br />
**[[1n5g]], [[1k0p]], [[1k18]] - hDpo α zinc finger domain – NMR<br />


*DNA polymerase beta
*DNA polymerase β


**[[4p4m]], [[4p4o]], [[4p4p]] - Dpo β + DNA + nucleotide – ''Leishmania infantum''<br />
**[[4p4m]], [[4p4o]], [[4p4p]] - Dpo β + DNA + nucleotide – ''Leishmania infantum''<br />
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**[[3au6]], [[3auo]] – TtDpo β + GTP + DNA<br />
**[[3au6]], [[3auo]] – TtDpo β + GTP + DNA<br />


*DNA polymerase gamma
*DNA polymerase γ


**[[3ikm]] - hDpo γ1+ γ2 <br />
**[[3ikm]] - hDpo γ1+ γ2 <br />
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**[[3mgi]], [[3hw8]], [[3hwt]], [[3hx0]], [[2pfo]], [[2pfp]], [[2pfq]] - hDpo λ (mutant) + DNA + nucleotide<br />
**[[3mgi]], [[3hw8]], [[3hwt]], [[3hx0]], [[2pfo]], [[2pfp]], [[2pfq]] - hDpo λ (mutant) + DNA + nucleotide<br />


*DNA polymerase delta
*DNA polymerase δ


**[[3e0j]] - hDpo δ2+ δ3<br />
**[[3e0j]] - hDpo δ2+ δ3<br />
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**[[4fo6]] - hDpo δ (mutant) + DNA + nucleotide analog<br />
**[[4fo6]] - hDpo δ (mutant) + DNA + nucleotide analog<br />


*DNA polymerase zeta
*DNA polymerase ζ


**[[3abd]], [[3abe]] - hDpo ζ catalytic subunit Rev3 + mitotic spindle assembly checkpoint protein Rev7<br />
**[[3abd]], [[3abe]] - hDpo ζ catalytic subunit Rev3 + mitotic spindle assembly checkpoint protein Rev7<br />
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**[[4fjo]], [[4gk5]] - hDpo κ + hDpo  ζ  catalytic subunit + DNA repair protein Rev1 + MAD2B<br />
**[[4fjo]], [[4gk5]] - hDpo κ + hDpo  ζ  catalytic subunit + DNA repair protein Rev1 + MAD2B<br />


*DNA polymerase eta
*DNA polymerase η


**[[2i5o]] - hDpo η ubiquitin-binding zinc finger – NMR<br />
**[[2i5o]] - hDpo η ubiquitin-binding zinc finger – NMR<br />
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**[[5aga]] - hDpo η + nucleotide<br />
**[[5aga]] - hDpo η + nucleotide<br />


*DNA polymerase iota
*DNA polymerase ι


**[[3q8r]], [[3q8s]], [[3h4b]], [[3h4d]], [[3gv5]], [[3gv7]], [[3gv8]], [[3epg]], [[3epi]], [[2fll]], [[2fln]], [[2flp]], [[2dpi]], [[2dpj]], [[2alz]], [[1zet]], [[1t3n]], [[4ebc]], [[4ebd]], [[4ebe]], [[4fs1]], [[4fs2]], [[4eyh]], [[4eyi]], [[3g6v]], [[3g6x]], [[3g6y]] - hDpo ι + DNA + nucleotide<br />
**[[3q8r]], [[3q8s]], [[3h4b]], [[3h4d]], [[3gv5]], [[3gv7]], [[3gv8]], [[3epg]], [[3epi]], [[2fll]], [[2fln]], [[2flp]], [[2dpi]], [[2dpj]], [[2alz]], [[1zet]], [[1t3n]], [[4ebc]], [[4ebd]], [[4ebe]], [[4fs1]], [[4fs2]], [[4eyh]], [[4eyi]], [[3g6v]], [[3g6x]], [[3g6y]] - hDpo ι + DNA + nucleotide<br />
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**[[3ai4]] - mDpo ι/yEGFP<br />
**[[3ai4]] - mDpo ι/yEGFP<br />


*DNA polymerase kappa
*DNA polymerase κ


**[[1t94]] - hDpo κ<br />
**[[1t94]] - hDpo κ<br />
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**[[2lsk]] - mDpo κ + DNA repair protein Rev1<br />
**[[2lsk]] - mDpo κ + DNA repair protein Rev1<br />


*DNA polymerase mu
*DNA polymerase μ


**[[2htf]], [[2dun]] - hDpo μ BRCT domain – NMR<br />
**[[2htf]], [[2dun]] - hDpo μ BRCT domain – NMR<br />
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**[[4xvi]], [[4xvk]], [[4xvl]], [[4xvm]] – hDpo ν catalytic domain + DNA<br />
**[[4xvi]], [[4xvk]], [[4xvl]], [[4xvm]] – hDpo ν catalytic domain + DNA<br />


*DNA polymerase chi
*DNA polymerase χ


**[[2m2t]] – AsfvDpo X – African swine fever virus – NMR<br />
**[[2m2t]] – AsfvDpo X – African swine fever virus – NMR<br />
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<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]
==External Links==

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