HOME
The Info List - DNA Polymerase


--- Advertisement ---



In molecular biology, DNA
DNA
polymerases are enzymes that synthesize DNA molecules from deoxyribonucleotides, the building blocks of DNA. These enzymes are essential for DNA
DNA
replication and usually work in pairs to create two identical DNA
DNA
strands from a single original DNA
DNA
molecule. During this process, DNA
DNA
polymerase "reads" the existing DNA
DNA
strands to create two new strands that match the existing ones.[1][2][3][4][5][6] These enzymes catalyze the following chemical reaction

deoxynucleoside triphosphate + DNAn ⇌ diphosphate + DNAn+1

DNA
DNA
polymerase adds nucleotides to the 3'- end of a DNA
DNA
strand, one nucleotide at a time. Every time a cell divides, DNA
DNA
polymerases are required to help duplicate the cell's DNA, so that a copy of the original DNA
DNA
molecule can be passed to each daughter cell. In this way, genetic information is passed down from generation to generation. Before replication can take place, an enzyme called helicase unwinds the DNA
DNA
molecule from its tightly woven form, in the process breaking the hydrogen bonds between the nucleotide bases. This opens up or "unzips" the double-stranded DNA
DNA
to give two single strands of DNA that can be used as templates for replication.

Contents

1 History 2 Function

2.1 Structure 2.2 Processivity

3 Variation across species

3.1 Prokaryotic Polymerase

3.1.1 Pol I 3.1.2 Pol II 3.1.3 Pol III 3.1.4 Pol IV 3.1.5 Pol V

3.2 Eukaryotic DNA
DNA
polymerase

3.2.1 Polymerases β, λ, σ and μ (beta, lambda, sigma, and mu) 3.2.2 Polymerases α, δ and ε (alpha, delta, and epsilon) 3.2.3 Polymerases η, ι and κ (eta, iota, and kappa) 3.2.4 Polymerases Rev1 and ζ (zeta) 3.2.5 Telomerase 3.2.6 Polymerases γ and θ (gamma and theta) 3.2.7 Polymerase
Polymerase
ν (nu) 3.2.8 Reverse transcriptase

4 See also 5 References 6 Further reading 7 External links

History[edit] In 1956, Arthur Kornberg
Arthur Kornberg
and colleagues discovered DNA
DNA
polymerase I (Pol I), in Escherichia coli. They described the DNA
DNA
replication process by which DNA
DNA
polymerase copies the base sequence of a template DNA
DNA
strand. Kornberg was later awarded the Nobel Prize in Physiology or Medicine in 1959 for this work.[7] DNA
DNA
polymerase II was also discovered by Thomas Kornberg (the son of Arthur Kornberg)[8] and Malcolm E. Gefter in 1970 while further elucidating the role of Pol I in E. coli DNA
DNA
replication.[9] Function[edit]

DNA
DNA
polymerase moves along the old strand in the 3'-5' direction, creating a new strand having a 5'-3'
5'-3'
direction.

DNA
DNA
polymerase with proofreading ability

The main function of DNA
DNA
polymerase is to synthesize DNA
DNA
from deoxyribonucleotides, the building blocks of DNA. The DNA
DNA
copies are created by the pairing of nucleotides to bases present on each strand of the original DNA
DNA
molecule. This pairing always occurs in specific combinations, with cytosine along with guanine, and thymine along with adenine, forming two separate pairs, respectively. By contrast, RNA polymerases synthesize RNA
RNA
from ribonucleotides from either RNA
RNA
or DNA. When synthesizing new DNA, DNA
DNA
polymerase can add free nucleotides only to the 3' end of the newly forming strand. This results in elongation of the newly forming strand in a 5'-3'
5'-3'
direction. No known DNA
DNA
polymerase is able to begin a new chain (de novo); it can only add a nucleotide onto a pre-existing 3'-OH group, and therefore needs a primer at which it can add the first nucleotide. Primers consist of RNA
RNA
or DNA
DNA
bases (or both). In DNA
DNA
replication, the first two bases are always RNA, and are synthesized by another enzyme called primase. Helicase
Helicase
and topoisomerase II are required to unwind DNA
DNA
from a double-strand structure to a single-strand structure to facilitate replication of each strand consistent with the semiconservative model of DNA
DNA
replication. It is important to note that the directionality of the newly forming strand (the daughter strand) is opposite to the direction in which DNA polymerase moves along the template strand. Since DNA
DNA
polymerase requires a free 3' OH group for initiation of synthesis, it can synthesize in only one direction by extending the 3' end of the preexisting nucleotide chain. Hence, DNA
DNA
polymerase moves along the template strand in a 3'-5' direction, and the daughter strand is formed in a 5'-3'
5'-3'
direction. This difference enables the resultant double-strand DNA
DNA
formed to be composed of two DNA
DNA
strands that are antiparallel to each other. The function of DNA
DNA
polymerase is not quite perfect, with the enzyme making about one mistake for every billion base pairs copied. Error correction is a property of some, but not all DNA
DNA
polymerases. This process corrects mistakes in newly synthesized DNA. When an incorrect base pair is recognized, DNA
DNA
polymerase moves backwards by one base pair of DNA. The 3'-5' exonuclease activity of the enzyme allows the incorrect base pair to be excised (this activity is known as proofreading). Following base excision, the polymerase can re-insert the correct base and replication can continue forwards. This preserves the integrity of the original DNA
DNA
strand that is passed onto the daughter cells. Fidelity is very important in DNA
DNA
replication. Mismatches in DNA
DNA
base pairing can potentially result in dysfunctional proteins and could lead to cancer. Many DNA
DNA
polymerase contain an exonuclease domain, which acts in detecting base pair mismatches and further performs in the removal of the incorrect nucleotide to be replaced by the correct one.[10] The shape and the interactions accommodating the Watson and Crick base pair are what primarily contribute to the detection or error. Hydrogen bonds play a key role in base pair binding and interaction. The loss of an interaction, which occurs at a mismatch, is said to trigger a shift in the balance, for the binding of the template-primer, from the polymerase, to the exonuclease domain. In addition, an incorporation of a wrong nucleotide causes a retard in DNA
DNA
polymerization. This delay gives time for the DNA
DNA
to be switched from the polymerase site to the exonuclease site. Different conformational changes and loss of interaction occur at different mismatches. In a purine:pyrimidine mismatch there is a displacement of the pyrimidine towards the major groove and the purine towards the minor groove. Relative to the shape of DNA
DNA
polymerase’s binding pocket, steric clashes occur between the purine and residues in the minor groove, and important van der Waals and electrostatic interactions are lost by the pyrimidine.[11] Pyrimidine:pyrimidine and purine:purine mismatches present less notable changes since the bases are displaced towards the major groove, and less steric hindrance is experienced. However, although the different mismatches result in different steric properties, DNA
DNA
polymerase is still able to detect and differentiate them so uniformly and maintain fidelity in DNA replication.[12] DNA
DNA
polymerization is also critical for many mutagenesis processes and is widely employed in biotechnologies. Structure[edit] The known DNA
DNA
polymerases have highly conserved structure, which means that their overall catalytic subunits vary very little from species to species, independent of their domain structures. Conserved structures usually indicate important, irreplaceable functions of the cell, the maintenance of which provides evolutionary advantages. The shape can be described as resembling a right hand with thumb, finger, and palm domains. The palm domain appears to function in catalyzing the transfer of phosphoryl groups in the phosphoryl transfer reaction. DNA is bound to the palm when the enzyme is active. This reaction is believed to be catalyzed by a two-metal-ion mechanism. The finger domain functions to bind the nucleoside triphosphates with the template base. The thumb domain plays a potential role in the processivity, translocation, and positioning of the DNA.[13] Processivity[edit] DNA
DNA
polymerase’s rapid catalysis is due to its processive nature. Processivity is a characteristic of enzymes that function on polymeric substrates. In the case of DNA
DNA
polymerase, the degree of processivity refers to the average number of nucleotides added each time the enzyme binds a template. The average DNA
DNA
polymerase requires about one second locating and binding a primer/template junction. Once it is bound, a nonprocessive DNA
DNA
polymerase adds nucleotides at a rate of one nucleotide per second.[14]:207–208 Processive DNA
DNA
polymerases, however, add multiple nucleotides per second, drastically increasing the rate of DNA
DNA
synthesis. The degree of processivity is directly proportional to the rate of DNA
DNA
synthesis. The rate of DNA
DNA
synthesis in a living cell was first determined as the rate of phage T4 DNA elongation in phage infected E. coli. During the period of exponential DNA
DNA
increase at 37 °C, the rate was 749 nucleotides per second.[15] DNA
DNA
polymerase’s ability to slide along the DNA
DNA
template allows increased processivity. There is a dramatic increase in processivity at the replication fork. This increase is facilitated by the DNA polymerase’s association with proteins known as the sliding DNA clamp. The clamps are multiple protein subunits associated in the shape of a ring. Using the hydrolysis of ATP, a class of proteins known as the sliding clamp loading proteins open up the ring structure of the sliding DNA
DNA
clamps allowing binding to and release from the DNA strand. Protein-protein interaction
Protein-protein interaction
with the clamp prevents DNA polymerase from diffusing from the DNA
DNA
template, thereby ensuring that the enzyme binds the same primer/template junction and continues replication.[14]:207–208 DNA
DNA
polymerase changes conformation, increasing affinity to the clamp when associated with it and decreasing affinity when it completes the replication of a stretch of DNA
DNA
to allow release from the clamp. Variation across species[edit]

DNA
DNA
polymerase family A

c:o6-methyl-guanine pair in the polymerase-2 basepair position

Identifiers

Symbol DNA_pol_A

Pfam PF00476

InterPro IPR001098

SMART -

PROSITE PDOC00412

SCOP 1dpi

SUPERFAMILY 1dpi

Available protein structures:

Pfam structures

PDB RCSB PDB; PDBe; PDBj

PDBsum structure summary

DNA
DNA
polymerase family B

crystal structure of rb69 gp43 in complex with dna containing thymine glycol

Identifiers

Symbol DNA_pol_B

Pfam PF00136

Pfam
Pfam
clan CL0194

InterPro IPR006134

PROSITE PDOC00107

SCOP 1noy

SUPERFAMILY 1noy

Available protein structures:

Pfam structures

PDB RCSB PDB; PDBe; PDBj

PDBsum structure summary

DNA
DNA
polymerase type B, organellar and viral

phi29 dna polymerase, orthorhombic crystal form, ssdna complex

Identifiers

Symbol DNA_pol_B_2

Pfam PF03175

Pfam
Pfam
clan CL0194

InterPro IPR004868

Available protein structures:

Pfam structures

PDB RCSB PDB; PDBe; PDBj

PDBsum structure summary

Based on sequence homology, DNA
DNA
polymerases can be further subdivided into seven different families: A, B, C, D, X, Y, and RT. Some viruses also encode special DNA
DNA
polymerases, such as Hepatitis B virus DNA
DNA
polymerase. These may selectively replicate viral DNA through a variety of mechanisms. Retroviruses
Retroviruses
encode an unusual DNA polymerase called reverse transcriptase, which is an RNA-dependent DNA polymerase (RdDp). It polymerizes DNA
DNA
from a template of RNA.

Family Types of DNA
DNA
polymerase Species Examples

A Replicative and Repair Polymerases Eukaryotic and Prokaryotic T7 DNA
DNA
polymerase, Pol I, and DNA
DNA
Polymerase
Polymerase
γ

B Replicative and Repair Polymerases Eukaryotic and Prokaryotic Pol II, Pol B, Pol ζ, Pol α, δ, and ε

C Replicative Polymerases Prokaryotic Pol III

D Replicative Polymerases Euryarchaeota Not well-characterized

X Replicative and Repair Polymerases Eukaryotic Pol β, Pol σ, Pol λ, Pol μ, and Terminal deoxynucleotidyl transferase

Y Replicative and Repair Polymerases Eukaryotic and Prokaryotic Pol ι (iota), Pol κ (kappa), Pol η (eta),[16] Pol IV, and Pol V

RT Replicative and Repair Polymerases Viruses, Retroviruses, and Eukaryotic Telomerase, Hepatitis B virus

Prokaryotic Polymerase Prokaryotes
Prokaryotes
only have one RNA polymerase
RNA polymerase
and it exists in two forms: core polymerase and holoenzyme. Core polymerase synthesizes DNA
DNA
from the DNA
DNA
template but it cannot initiate the synthesis alone or accurately. Holoenzyme accurately initiates synthesis. Prokaryotic Polymerase[edit] Pol I[edit] Prokaryotic family A polymerases include the DNA
DNA
polymerase I (Pol I) enzyme, which is encoded by the polA gene and ubiquitous among prokaryotes. This repair polymerase is involved in excision repair with both 3'-5' and 5'-3'
5'-3'
exonuclease activity and processing of Okazaki fragments
Okazaki fragments
generated during lagging strand synthesis.[17] Pol I is the most abundant polymerase, accounting for >95% of polymerase activity in E. coli; yet cells lacking Pol I have been found suggesting Pol I activity can be replaced by the other four polymerases. Pol I adds ~15-20 nucleotides per second, thus showing poor processivity. Instead, Pol I starts adding nucleotides at the RNA primer:template junction known as the origin of replication (ori). Approximately 400 bp downstream from the origin, the Pol III holoenzyme is assembled and takes over replication at a highly processive speed and nature.[18] Pol II[edit] DNA
DNA
polymerase II, a family B polymerase, is a polB gene product also known as DnaA. Pol II has 3'-5' exonuclease activity and participates in DNA
DNA
repair, replication restart to bypass lesions, and its cell presence can jump from ~30-50 copies per cell to ~200-300 during SOS induction. Pol II is also thought to be a backup to Pol III as it can interact with holoenzyme proteins and assume a high level of processivity. The main role of Pol II is thought to be the ability to direct polymerase activity at the replication fork and helped stalled Pol III bypass terminal mismatches.[19] Pol III[edit] DNA
DNA
polymerase III holoenzyme is the primary enzyme involved in DNA replication in E. coli and belongs to family C polymerases. It consists of three assemblies: the pol III core, the beta sliding clamp processivity factor, and the clamp-loading complex. The core consists of three subunits: α, the polymerase activity hub, ɛ, exonucleolytic proofreader, and θ, which may act as a stabilizer for ɛ. The holoenzyme contains two cores, one for each strand, the lagging and leading.[19] The beta sliding clamp processivity factor is also present in duplicate, one for each core, to create a clamp that encloses DNA
DNA
allowing for high processivity.[20] The third assembly is a seven-subunit (τ2γδδ′χψ) clamp loader complex. Recent research has classified Family C polymerases as a subcategory of Family X with no eukaryotic equivalents.[21] Pol IV[edit] In E. coli, DNA
DNA
polymerase IV (Pol 4) is an error-prone DNA
DNA
polymerase involved in non-targeted mutagenesis.[22] Pol IV is a Family Y polymerase expressed by the dinB gene that is switched on via SOS induction caused by stalled polymerases at the replication fork. During SOS induction, Pol IV production is increased tenfold and one of the functions during this time is to interfere with Pol III holoenzyme processivity. This creates a checkpoint, stops replication, and allows time to repair DNA
DNA
lesions via the appropriate repair pathway.[23] Another function of Pol IV is to perform translesion synthesis at the stalled replication fork like, for example, bypassing N2-deoxyguanine adducts at a faster rate than transversing undamaged DNA. Cells lacking dinB gene have a higher rate of mutagenesis caused by DNA
DNA
damaging agents.[24] Pol V[edit] DNA
DNA
polymerase V (Pol V) is a Y-family DNA
DNA
polymerase that is involved in SOS response
SOS response
and translesion synthesis DNA
DNA
repair mechanisms.[25] Transcription of Pol V via the umuDC genes is highly regulated to produce only Pol V when damaged DNA
DNA
is present in the cell generating an SOS response. Stalled polymerases causes RecA to bind to the ssDNA, which causes the LexA protein to autodigest. LexA then loses its ability to repress the transcription of the umuDC operon. The same RecA-ss DNA
DNA
nucleoprotein posttranslationally modifies the UmuD protein into UmuD' protein. UmuD and UmuD' form a heterodimer that interacts with UmuC, which in turn activates umuC's polymerase catalytic activity on damaged DNA.[26] Interestingly, In E. coli, a polymerase “tool belt” model for switching pol III with pol IV at a stalled replication fork, where both polymerases bind simultaneously to the β-clamp, has been proposed.[27] However, the involvement of more than one TLS polymerase working in succession to bypass a lesion has not yet been shown in E. coli. Moreover, Pol IV can catalyze both insertion and extension with high efficiency, whereas pol V is considered the major SOS TLS polymerase. One example is the bypass of intra strand guanine thymine cross-link where it was shown on the basis of the difference in the mutational signatures of the two polymerases, that pol IV and pol V compete for TLS of the intra-strand crosslink.[27] Eukaryotic DNA
DNA
polymerase[edit] Polymerases β, λ, σ and μ (beta, lambda, sigma, and mu)[edit] Family X polymerases contain the well-known eukaryotic polymerase pol β (beta), as well as other eukaryotic polymerases such as Pol σ (sigma), Pol λ (lambda), Pol μ (mu), and Terminal deoxynucleotidyl transferase (TdT). Family X polymerases are found mainly in vertebrates, and a few are found in plants and fungi. These polymerases have highly conserved regions that include two helix-hairpin-helix motifs that are imperative in the DNA-polymerase interactions. One motif is located in the 8 kDa domain that interacts with downstream DNA
DNA
and one motif is located in the thumb domain that interacts with the primer strand. Pol β, encoded by POLB gene, is required for short-patch base excision repair, a DNA
DNA
repair pathway that is essential for repairing alkylated or oxidized bases as well as abasic sites. Pol λ and Pol μ, encoded by the POLL
POLL
and POLM
POLM
genes respectively, are involved in non-homologous end-joining, a mechanism for rejoining DNA
DNA
double-strand breaks due to hydrogen peroxide and ionizing radiation, respectively. TdT is expressed only in lymphoid tissue, and adds "n nucleotides" to double-strand breaks formed during V(D)J recombination
V(D)J recombination
to promote immunological diversity.[28] Polymerases α, δ and ε (alpha, delta, and epsilon)[edit] Pol α (alpha), Pol δ (delta), and Pol ε (epsilon) are members of Family B Polymerases and are the main polymerases involved with nuclear DNA
DNA
replication. Pol α complex (pol α- DNA
DNA
primase complex) consists of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the small and the large primase subunits PRIM1
PRIM1
and PRIM2
PRIM2
respectively. Once primase has created the RNA
RNA
primer, Pol α starts replication elongating the primer with ~20 nucleotides.[29] Due to its high processivity, Pol δ takes over the leading and lagging strand synthesis from Pol α.[14]:218–219 Pol δ is expressed by genes POLD1, creating the catalytic subunit, POLD2, POLD3, and POLD4 creating the other subunits that interact with Proliferating Cell Nuclear Antigen (PCNA), which is a DNA
DNA
clamp that allows Pol δ to possess processivity.[30] Pol ε is encoded by the POLE1, the catalytic subunit, POLE2, and POLE3
POLE3
gene. It has been reported that the function of Pol ε is to extend the leading strand during replication, while Pol δ primarily replicates the lagging strand; however, recent evidence suggested that Pol δ might have a role in replicating the leading strand of DNA
DNA
as well.[31] Pol ε's C-terminus region is thought to be essential to cell vitality as well. The C-terminus region is thought to provide a checkpoint before entering anaphase, provide stability to the holoenzyme, and add proteins to the holoenzyme necessary for initiation of replication.[32] Polymerases η, ι and κ (eta, iota, and kappa)[edit] Pol η (eta), Pol ι (iota), and Pol κ (kappa), are Family Y DNA polymerases involved in the DNA
DNA
repair by translesion synthesis and encoded by genes POLH, POLI, and POLK
POLK
respectively. Members of Family Y have five common motifs to aid in binding the substrate and primer terminus and they all include the typical right hand thumb, palm and finger domains with added domains like little finger (LF), polymerase-associated domain (PAD), or wrist. The active site, however, differs between family members due to the different lesions being repaired. Polymerases in Family Y are low-fidelity polymerases, but have been proven to do more good than harm as mutations that affect the polymerase can cause various diseases, such as skin cancer and Xeroderma Pigmentosum Variant (XPS). The importance of these polymerases is evidenced by the fact that gene encoding DNA
DNA
polymerase η is referred as XPV, because loss of this gene results in the disease Xeroderma Pigmentosum Variant. Pol η is particularly important for allowing accurate translesion synthesis of DNA
DNA
damage resulting from ultraviolet radiation. The functionality of Pol κ is not completely understood, but researchers have found two probable functions. Pol κ is thought to act as an extender or an inserter of a specific base at certain DNA
DNA
lesions. All three translesion synthesis polymerases, along with Rev1, are recruited to damaged lesions via stalled replicative DNA
DNA
polymerases. There are two pathways of damage repair leading researchers to conclude that the chosen pathway depends on which strand contains the damage, the leading or lagging strand.[33] Polymerases Rev1 and ζ (zeta)[edit] Pol ζ another B family polymerase, is made of two subunits Rev3, the catalytic subunit, and Rev7, which increases the catalytic function of the polymerase, and is involved in translesion synthesis. Pol ζ lacks 3' to 5' exonuclease activity, is unique in that it can extend primers with terminal mismatches. Rev1 has three regions of interest in the BRCT domain, ubiquitin-binding domain, and C-terminal domain and has dCMP transferase ability, which adds deoxycytidine opposite lesions that would stall replicative polymerases Pol δ and Pol ε. These stalled polymerases activate ubiquitin complexes that in turn disassociate replication polymerases and recruit Pol ζ and Rev1. Together Pol ζ and Rev1 add deoxycytidine and Pol ζ extends past the lesion. Through a yet undetermined process, Pol ζ disassociates and replication polymerases reassociate and continue replication. Pol ζ and Rev1 are not required for replication, but loss of REV3 gene in budding yeast can cause increased sensitivity to DNA-damaging agents due to collapse of replication forks where replication polymerases have stalled.[34] Telomerase[edit] Telomerase
Telomerase
is a ribonucleoprotein recruited to replicate ends of linear chromosomes because normal DNA
DNA
polymerase cannot replicate the ends, or telomere. The single-strand 3’ overhang of the double-strand chromosome with the sequence 5’-TTAGGG-3’ recruits telomerase. Telomerase
Telomerase
acts like other DNA
DNA
polymerases by extending the 3’ end, but, unlike other DNA
DNA
polymerases, telomerase does not require a template. The TERT subunit, an example of a reverse transcriptase, uses the RNA
RNA
subunit to form the primer–template junction that allows telomerase to extend the 3’ end of chromosome ends. The gradual decrease in size of telomeres as the result of many replications over a lifetime are thought to be associated with the effects of aging.[14]:248–249 Polymerases γ and θ (gamma and theta)[edit] Pol γ (gamma) and Pol θ (theta) are Family A polymerases. Pol γ, encoded by the POLG
POLG
gene, is the only mt DNA
DNA
polymerase and therefore replicates, repairs, and has proofreading 3'-5' exonuclease and 5' dRP lyase activities. Any mutation that leads to limited or non-functioning Pol γ has a significant effect on mt DNA
DNA
and is the most common cause of autosomal inherited mitochondrial disorders.[35] Pol γ contains a C-terminus polymerase domain and an N-terminus 3'-5' exonuclease domain that are connected via the linker region, which binds the accessory subunit. The accessory subunit binds DNA
DNA
and is required for processivity of Pol γ. Point mutation A467T in the linker region is responsible for more than one-third of all Pol γ-associated mitochondrial disorders.[36] While many homologs of Pol θ, encoded by the POLQ
POLQ
gene, are found in eukaryotes, its function is not clearly understood. The sequence of amino acids in the C-terminus is what classifies Pol θ as Family A polymerase, although the error rate for Pol θ is more closely related to Family Y polymerases. Pol θ extends mismatched primer termini and can bypass abasic sites by adding a nucleotide. It also has Deoxyribophosphodiesterase (dRPase) activity in the polymerase domain and can show ATPase
ATPase
activity in close proximity to ssDNA.[37] Polymerase
Polymerase
ν (nu)[edit] Further information: DNA
DNA
polymerase nu Reverse transcriptase[edit] Retroviruses
Retroviruses
encode an unusual DNA
DNA
polymerase called reverse transcriptase, which is an RNA-dependent DNA
DNA
polymerase (RdDp) that synthesizes DNA
DNA
from a template of RNA. The reverse transcriptase family contain both DNA
DNA
polymerase functionality and RNase H functionality, which degrades RNA
RNA
base-paired to DNA. An example of a retrovirus is HIV.[14]: See also[edit]

Biological machines DNA
DNA
repair DNA
DNA
replication DNA
DNA
sequencing Enzyme
Enzyme
catalysis Genetic recombination Molecular cloning Polymerase
Polymerase
chain reaction Protein
Protein
domain dynamics Reverse transcription RNA
RNA
polymerase Taq DNA
DNA
polymerase

References[edit]

^ Bollum FJ (August 1960). "Calf thymus polymerase". The Journal of Biological Chemistry. 235: 2399–403. PMID 13802334.  ^ Falaschi A, Kornberg A (April 1966). "Biochemical studies of bacterial sporulation. II. Deoxy- ribonucleic acid polymerase in spores of Bacillus subtilis". The Journal of Biological Chemistry. 241 (7): 1478–82. PMID 4957767.  ^ Lehman IR, Bessman MJ, Simms ES, Kornberg A (July 1958). "Enzymatic synthesis of deoxyribonucleic acid. I. Preparation of substrates and partial purification of an enzyme from Escherichia coli". The Journal of Biological Chemistry. 233 (1): 163–70. PMID 13563462.  ^ Richardson CC, Schildkraut CL, Aposhian HV, Kornberg A (January 1964). "Enzymatic synthesis of deoxyribonucleic acid. XIV. Further purification and properties of deoxyribonucleic acid polymerase of Escherichia coli". The Journal of Biological Chemistry. 239: 222–32. PMID 14114848.  ^ Schachman HK, Adler J, Radding CM, Lehman IR, Kornberg A (November 1960). "Enzymatic synthesis of deoxyribonucleic acid. VII. Synthesis of a polymer of deoxyadenylate and deoxythymidylate". The Journal of Biological Chemistry. 235: 3242–9. PMID 13747134.  ^ Zimmerman BK (May 1966). "Purification and properties of deoxyribonucleic acid polymerase from Micrococcus lysodeikticus". The Journal of Biological Chemistry. 241 (9): 2035–41. PMID 5946628.  ^ "The Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
1959". Nobel Foundation. Retrieved December 1, 2012.  ^ " DNA
DNA
polymerase III holoenzyme".. Retrieved April 4, 2017.  ^ Tessman I, Kennedy MA (February 1994). " DNA
DNA
polymerase II of Escherichia coli
Escherichia coli
in the bypass of abasic sites in vivo". Genetics. 136 (2): 439–48. PMC 1205799 . PMID 7908652.  ^ Garrett, Grisham (2013). Biochemistry. Mary Finch.  ^ Hunter WN, Brown T, Anand NN, Kennard O (1986). "Structure of an adenine-cytosine base pair in DNA
DNA
and its implications for mismatch repair". Nature. 320 (6062): 552–5. Bibcode:1986Natur.320..552H. doi:10.1038/320552a0. PMID 3960137.  ^ Swan MK, Johnson RE, Prakash L, Prakash S, Aggarwal AK (September 2009). "Structural basis of high-fidelity DNA
DNA
synthesis by yeast DNA polymerase delta". Nature Structural & Molecular Biology. 16 (9): 979–86. doi:10.1038/nsmb.1663. PMC 3055789 . PMID 19718023.  ^ Steitz TA (June 1999). " DNA
DNA
polymerases: structural diversity and common mechanisms". The Journal of Biological Chemistry. 274 (25): 17395–8. doi:10.1074/jbc.274.25.17395. PMID 10364165.  ^ a b c d e Losick R, Watson JD, Baker TA, Bell S, Gann A, Levine MW (2008). Molecular biology
Molecular biology
of the gene (6th ed.). San Francisco: Pearson/Benjamin Cummings. ISBN 0-8053-9592-X.  ^ McCarthy D, Minner C, Bernstein H, Bernstein C (October 1976). "DNA elongation rates and growing point distributions of wild-type phage T4 and a DNA-delay amber mutant". Journal of Molecular Biology. 106 (4): 963–81. doi:10.1016/0022-2836(76)90346-6. PMID 789903.  ^ Boehm EM, Powers KT, Kondratick CM, Spies M, Houtman JC, Washington MT (April 2016). "The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein
Protein
(PIP) Motif of DNA
DNA
Polymerase
Polymerase
η Mediates Its Interaction with the C-terminal Domain of Rev1". The Journal of Biological Chemistry. 291 (16): 8735–44. doi:10.1074/jbc.M115.697938. PMC 4861442 . PMID 26903512.  ^ Maga G, Hubscher U, Spadari S, Villani G (2010). DNA
DNA
Polymerases: Discovery, Characterization Functions in Cellular DNA
DNA
Transactions. World Scientific Publishing Company. ISBN 981-4299-16-2.  ^ Choi CH, Burton ZF, Usheva A (February 2004). "Auto-acetylation of transcription factors as a control mechanism in gene expression". Cell Cycle. 3 (2): 114–5. doi:10.4161/cc.3.2.651. PMID 14712067.  ^ a b Banach-Orlowska M, Fijalkowska IJ, Schaaper RM, Jonczyk P (October 2005). " DNA
DNA
polymerase II as a fidelity factor in chromosomal DNA
DNA
synthesis in Escherichia coli". Molecular Microbiology. 58 (1): 61–70. doi:10.1111/j.1365-2958.2005.04805.x. PMID 16164549.  ^ Olson MW, Dallmann HG, McHenry CS (December 1995). " DnaX complex of Escherichia coli
Escherichia coli
DNA
DNA
polymerase III holoenzyme. The chi psi complex functions by increasing the affinity of tau and gamma for delta.delta' to a physiologically relevant range". The Journal of Biological Chemistry. 270 (49): 29570–7. doi:10.1074/jbc.270.49.29570. PMID 7494000.  ^ " DNA
DNA
Polymerase
Polymerase
Families". News-medical.net. 2014-05-06. Retrieved 2014-06-28.  ^ Goodman MF (2002). "Error-prone repair DNA
DNA
polymerases in prokaryotes and eukaryotes". Annual Review of Biochemistry. 71: 17–50. doi:10.1146/annurev.biochem.71.083101.124707. PMID 12045089.  ^ Mori T, Nakamura T, Okazaki N, Furukohri A, Maki H, Akiyama MT (2012). " Escherichia coli
Escherichia coli
DinB inhibits replication fork progression without significantly inducing the SOS response". Genes & Genetic Systems. 87 (2): 75–87. doi:10.1266/ggs.87.75. PMID 22820381.  ^ Jarosz DF, Godoy VG, Walker GC (April 2007). "Proficient and accurate bypass of persistent DNA
DNA
lesions by DinB DNA
DNA
polymerases". Cell Cycle. 6 (7): 817–22. doi:10.4161/cc.6.7.4065. PMID 17377496.  ^ Patel M, Jiang Q, Woodgate R, Cox MM, Goodman MF (June 2010). "A new model for SOS-induced mutagenesis: how RecA protein activates DNA polymerase V". Critical Reviews in Biochemistry and Molecular Biology. 45 (3): 171–84. doi:10.3109/10409238.2010.480968. PMC 2874081 . PMID 20441441.  ^ Sutton MD, Walker GC (July 2001). "Managing DNA
DNA
polymerases: coordinating DNA
DNA
replication, DNA
DNA
repair, and DNA
DNA
recombination". Proceedings of the National Academy of Sciences of the United States of America. 98 (15): 8342–9. Bibcode:2001PNAS...98.8342S. doi:10.1073/pnas.111036998. PMC 37441 . PMID 11459973.  ^ a b Raychaudhury P, Basu AK (March 2011). "Genetic requirement for mutagenesis of the G[8,5-Me]T cross-link in Escherichia coli: DNA polymerases IV and V compete for error-prone bypass". Biochemistry. 50 (12): 2330–8. doi:10.1021/bi102064z. PMC 3062377 . PMID 21302943.  ^ Yamtich J, Sweasy JB (May 2010). " DNA
DNA
polymerase family X: function, structure, and cellular roles". Biochimica et Biophysica Acta. 1804 (5): 1136–50. doi:10.1016/j.bbapap.2009.07.008. PMC 2846199 . PMID 19631767.  ^ Chansky ML, Marks A, Peet A (2012). Marks' Basic Medical Biochemistry: a clinical approach (4th ed.). Philadelphia: Wolter Kluwer Health/Lippincott Williams & Wilkins. p. chapter13. ISBN 160831572X.  ^ Chung DW, Zhang JA, Tan CK, Davie EW, So AG, Downey KM (December 1991). "Primary structure of the catalytic subunit of human DNA polymerase delta and chromosomal location of the gene". Proceedings of the National Academy of Sciences of the United States of America. 88 (24): 11197–201. Bibcode:1991PNAS...8811197C. doi:10.1073/pnas.88.24.11197. PMC 53101 . PMID 1722322.  ^ Johnson RE, Klassen R, Prakash L, Prakash S (July 2015). "A Major Role of DNA
DNA
Polymerase
Polymerase
δ in Replication of Both the Leading and Lagging DNA
DNA
Strands". Molecular Cell. 59 (2): 163–175. doi:10.1016/j.molcel.2015.05.038. PMC 4517859 . PMID 26145172.  ^ Edwards S, Li CM, Levy DL, Brown J, Snow PM, Campbell JL (April 2003). "Saccharomyces cerevisiae DNA
DNA
polymerase epsilon and polymerase sigma interact physically and functionally, suggesting a role for polymerase epsilon in sister chromatid cohesion". Molecular and Cellular Biology. 23 (8): 2733–48. doi:10.1128/mcb.23.8.2733-2748.2003. PMC 152548 . PMID 12665575.  ^ Ohmori H, Hanafusa T, Ohashi E, Vaziri C (2009). "Separate roles of structured and unstructured regions of Y-family DNA
DNA
polymerases". Advances in Protein
Protein
Chemistry and Structural Biology. Advances in Protein
Protein
Chemistry and Structural Biology. 78: 99–146. doi:10.1016/S1876-1623(08)78004-0. ISBN 9780123748270. PMC 3103052 . PMID 20663485.  ^ Gan GN, Wittschieben JP, Wittschieben BØ, Wood RD (January 2008). " DNA
DNA
polymerase zeta (pol zeta) in higher eukaryotes". Cell Research. 18 (1): 174–83. doi:10.1038/cr.2007.117. PMID 18157155.  ^ Zhang L, Chan SS, Wolff DJ (July 2011). "Mitochondrial disorders of DNA
DNA
polymerase γ dysfunction: from anatomic to molecular pathology diagnosis". Archives of Pathology & Laboratory Medicine. 135 (7): 925–34. doi:10.1043/2010-0356-RAR.1 (inactive 2017-01-31). PMC 3158670 . PMID 21732785.  ^ Stumpf JD, Copeland WC (January 2011). "Mitochondrial DNA replication and disease: insights from DNA
DNA
polymerase γ mutations". Cellular and Molecular Life Sciences. 68 (2): 219–33. doi:10.1007/s00018-010-0530-4. PMC 3046768 . PMID 20927567.  ^ Hogg M, Sauer-Eriksson AE, Johansson E (March 2012). "Promiscuous DNA
DNA
synthesis by human DNA
DNA
polymerase θ". Nucleic Acids Research. 40 (6): 2611–22. doi:10.1093/nar/gkr1102. PMC 3315306 . PMID 22135286. 

Further reading[edit]

Burgers PM, Koonin EV, Bruford E, Blanco L, Burtis KC, Christman MF, Copeland WC, Friedberg EC, Hanaoka F, Hinkle DC, Lawrence CW, Nakanishi M, Ohmori H, Prakash L, Prakash S, Reynaud CA, Sugino A, Todo T, Wang Z, Weill JC, Woodgate R (November 2001). "Eukaryotic DNA polymerases: proposal for a revised nomenclature". The Journal of Biological Chemistry. 276 (47): 43487–90. doi:10.1074/jbc.R100056200. PMID 11579108. 

External links[edit]

Wikimedia Commons has media related to DNA
DNA
polymerases.

DNA
DNA
polymerases at the US National Library of Medicine Medical Subject Headings (MeSH) PDB Molecule
Molecule
of the Month DNA
DNA
polymerase Unusual repair mechanism in DNA
DNA
polymerase lambda, Ohio State University, July 25, 2006. A great animation of DNA
DNA
Polymerase
Polymerase
from WEHI at 1:45 minutes in 3D macromolecular structures of DNA
DNA
polymerase from the EM Data Bank(EMDB)

v t e

DNA
DNA
replication (comparing Prokaryotic to Eukaryotic)

Initiation

Prokaryotic (initiation)

Pre-replication complex

dnaC

Cdc6

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
DNA
polymerase III holoenzyme

dnaC dnaE dnaH dnaN dnaQ dnaT dnaX holA holB holC holD holE

Replisome DNA
DNA
ligase DNA
DNA
clamp Topoisomerase

DNA
DNA
gyrase

Prokaryotic DNA
DNA
polymerase: DNA
DNA
polymerase I

Klenow fragment

Eukaryotic (synthesis in S phase)

Replication factor C

RFC1

Flap endonuclease

FEN1

Topoisomerase Replication protein A

RPA1

Eukaryotic DNA
DNA
polymerase: alpha

POLA1 POLA2 PRIM1 PRIM2

delta

POLD1 POLD2 POLD3 POLD4

epsilon

POLE POLE2 POLE3 POLE4

DNA
DNA
clamp

PCNA

Control of chromosome duplication

Both

Movement: Processivity DNA
DNA
ligase

Termination

Telomere: Telomerase

TERT TERC DKC1

v t e

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)

Ribose-phosphate diphosphokinase Thiamine diphosphokinase

2.7.7: nucleotidyltransferase (PO4-nucleoside)

Polymerase

DNA
DNA
polymerase

DNA-directed DNA
DNA
polymerase I II III IV V

RNA-directed DNA
DNA
polymerase Reverse transcriptase

Telomerase

DNA
DNA
nucleotidylexotransferase/Terminal deoxynucleotidyl transferase

RNA
RNA
nucleotidyltransferase

RNA
RNA
polymerase/DNA-directed RNA
RNA
polymerase RNA polymerase
RNA polymerase
I II III IV V Primase RNA-dependent RNA
RNA
polymerase

PNPase

Phosphorolytic 3' to 5' exoribonuclease

RNase PH PNPase

Nucleotidyltransferase

UTP—glucose-1-phosphate uridylyltransferase Galactose-1-phosphate uridylyltransferase

Guanylyltransferase

m RNA
RNA
capping enzyme

Other

Recombinase (Integrase) Transposase

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
Enzyme
promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme
Enzyme
catalysis

Regulation

Allosteric regulation Cooperativity Enzyme
Enzyme
inhibitor

Classification

EC number Enzyme
Enzyme
superfamily Enzyme
Enzyme
family List of enzymes

Kinetics

Enzyme
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)

Molecular and Cellu

.