DNA polymerase: Difference between revisions

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==

====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.<ref name="ncbi" />  

====Terminal deoxynucleotidyl transferase====

<scene name='44/440019/Cv/7'>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.<ref name="ncbi" />  

====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.<ref name="ncbi" />

====DNA Polymerase V====

===Reverse Transcriptase===

The most commonly known Reverse Transcriptase DNA polymerase is HIV-1 Reverse Transcriptase. The reason this is so important to understand is that it is the target of anti-AIDS drugs. <ref>PMID: 7526780</ref> For detailed information on the RT family polymerases, see [[Reverse transcriptase]].

==Structure==

===Family Y===

The N-terminal of the Family Y polymerases contains the catalytic core of the fingers, palm, and thumb. The C-terminal, which has a conserved tertiary structure of a four-stranded beta sheet supported on one side by two alpha helices, otherwise referred to as the little finger domain, contributes to DNA binding and is essential for complete polymerase activity. This family lacks flexibility in the fingers subdomain, which is uncharacteristic of the other families. The other parts of the catalytic core and the little finger domain are flexible and frequently assume different positions. <ref>PMID: 20123134</ref>

==Mechanism==

The majority of DNA polymerases undergo a two-metal-ion mechanism. Two metal ions in the active site work to stabilize the pentacoordinated transition state. The first metal ion activates the hydroxyl groups. Those hydroxyl groups then go on to attack the phosphate group of the dNTP. The second metal ion not only stabilizes the negative charge, but also builds on the leaving oxygen and chelating phosphate groups. <ref name='SteitzJBiolChem1999'/>

Some Dpo terminology:<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 />

See also [[User:Karl E. Zahn/RB69 DNA polymerase (gp43)]]<br />