DNA polymerase: Difference between revisions
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====Polymerase γ==== | ====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 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.<ref name="ncbi">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391090/pdf/nihms-46213.pdf</ref> | ||
====Polymerase α, Polymerase δ, and Polymerase ε==== | ====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. | 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.<ref name="ncbi" /> | ||
====Family X==== | ====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]]. | 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.<ref name="ncbi" /> For more details see [[DNA polymerase beta]]. | ||
====Polymerases η, Polymerase ι, and Polymerase κ==== | ====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. | 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" /> | ||
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====DNA Polymerase I==== | ====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)]]. | [[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''.<ref name="ncbi" /> 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/4'>Octylglucoside binding site</scene> in Family A DNA polymerase I ([[1taq]]). | ||
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====DNA Polymerase II==== | ====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 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 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. | 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.<ref name="ncbi" /> | ||
For more details see [[Polymerase III homoenzyme beta subunit]] and [[Alpha Subunit of Thermus aquaticus DNA Polymerase III]]. | For more details see [[Polymerase III homoenzyme beta subunit]] and [[Alpha Subunit of Thermus aquaticus DNA Polymerase III]]. | ||
====DNA Polymerase IV==== | ====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 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==== | ====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. | 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.<ref name="ncbi" /> | ||
===Reverse Transcriptase=== | ===Reverse Transcriptase=== | ||
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<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
==External Links== | ==External Links== | ||
Revision as of 04:28, 7 May 2018
OverviewDNA 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.[1] The families are:
FunctionDNA polymerases are essential enzymes for DNA Replication.[1] 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 PolymeraseAccording to their sequence homology and 3D structure similarities, DNA Polymerases can be divided into 7 families: A, B, C, D, X, Y, and RT.[2]
Eukaryotic PolymerasePolymerase γPolymerase 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.[3] Polymerase α, Polymerase δ, and Polymerase εMembers 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.[3] Family XFamily 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.[3] For more details see DNA polymerase beta. Polymerases η, Polymerase ι, and Polymerase κPolymerase 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.[3]
Prokaryotic PolymeraseDNA Polymerase IDNA 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.[3] See also Taq DNA polymerase (Hebrew). in Family A DNA polymerase I (1taq). in Family A DNA polymerase I (1taq).[4] DNA Polymerase IIDNA 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.[3]
DNA Polymerase IIIDNA 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.[3] For more details see Polymerase III homoenzyme beta subunit and Alpha Subunit of Thermus aquaticus DNA Polymerase III. DNA Polymerase IVDNA 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.[3]
DNA Polymerase VDNA 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.[3] Reverse Transcriptase
Some Dpo terminology: Dpo sliding clamp is made of the complex of Dpo and Proliferating Cell Nuclear Antigen (PCNA) which encircles it.
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3D Structures of DNA polymerase3D Structures of DNA polymerase
Updated on 07-May-2018
ReferencesReferences
- ↑ Steitz TA. DNA polymerases: structural diversity and common mechanisms. J Biol Chem. 1999 Jun 18;274(25):17395-8. PMID:10364165
- ↑ Steitz TA. DNA polymerases: structural diversity and common mechanisms. J Biol Chem. 1999 Jun 18;274(25):17395-8. PMID:10364165
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391090/pdf/nihms-46213.pdf
- ↑ Kim Y, Eom SH, Wang J, Lee DS, Suh SW, Steitz TA. Crystal structure of Thermus aquaticus DNA polymerase. Nature. 1995 Aug 17;376(6541):612-6. PMID:7637814 doi:http://dx.doi.org/10.1038/376612a0