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drug target
R61 and S62 play key roles in the specificity and effectiveness of DNA polymerase eta for bypassing TTD lesions during DNA replication. Understanding the basis for this specificity is important for designing drugs aimed at cancer treatment
drug target
the enzyme is a viable antimalarial drug target
drug target
the enzyme is an attractive target for cancer therapies because it has been correlated with a shorter survival time in patients with glioblastoma as well as poor chemotherapy responses in some cases
evolution
compared to mammalian pol betas, the Danio rerio enzyme contains a P63D amino acid substitution. This substitution lies in a hairpin sequence within an 8-kDa domain, likely to be important in DNA binding
evolution
DNA polymerase I belongs to the DNA polymerase family A, all the functionally important regions in the polymerase active site of Geobacillus kaue polI are conserved, phylogenetic analysis, evolutionary relationship of diverse Geobacillus species, overview
evolution
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DNA polymerase ny is a conserved family A DNA polymerase
evolution
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human DNA polymerase lambda is a member of the DNA polymerase X family
evolution
K4PolI is a family A DNA polymerase, phylogenetic tree
evolution
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the catalytic subunits Pol1, Pol2 and Pol3 or isozymes pol alpha, pol epsilon, and pol delta are phylogenetically related, and belong to the class B DNA polymerases. The B subunits are all essential and share a phosphodiesterase-like and oligosaccharide binding domain. Eukaryotes contain a fourth class B DNA polymerase, Pol zeta, which is the major enzyme responsible for mutagenesis in response to DNA damage
evolution
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the enzyme belongs to the DNA polymerase family A
evolution
the enzyme belongs to the DNA polymerase family A
evolution
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the enzyme belongs to the DNA polymerase family B
evolution
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the enzyme belongs to the DNA polymerase Y-family, phylogenetic analysis
evolution
a self-activated mechanism for efficient polymerase catalysis is proposed, which is based on the identification of an evolutionary convergence to preserve a key enzymatic structural element in all the available X-ray structures of DNA/RNA polymerases from all domains of life
evolution
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the enzyme belongs to the DNA polymerase family A
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evolution
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DNA polymerase I belongs to the DNA polymerase family A, all the functionally important regions in the polymerase active site of Geobacillus kaue polI are conserved, phylogenetic analysis, evolutionary relationship of diverse Geobacillus species, overview
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evolution
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the enzyme belongs to the DNA polymerase family A
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evolution
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K4PolI is a family A DNA polymerase, phylogenetic tree
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evolution
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the catalytic subunits Pol1, Pol2 and Pol3 or isozymes pol alpha, pol epsilon, and pol delta are phylogenetically related, and belong to the class B DNA polymerases. The B subunits are all essential and share a phosphodiesterase-like and oligosaccharide binding domain. Eukaryotes contain a fourth class B DNA polymerase, Pol zeta, which is the major enzyme responsible for mutagenesis in response to DNA damage
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malfunction
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abo4 mutants show early flowering and reduced expression of flowering locus C and increased expression of flowering locus T with changing histone H3 modifications
malfunction
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cell lines downregulating poliota exhibit hypersensitivity to DNA damage induced by hydrogen peroxide or menadione but not to ethylmethane sulfonate, UVC or UVA, extracts from cells downregulating poliota show reduced base excision repair activity
malfunction
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class switch recombination is normal in mice deficient for pols theta and eta
malfunction
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depletion of Pol eta from undamaged human cells affects cell cycle progression (G2/M and proliferative defects) and the rate of cell proliferation and results in increased spontaneous chromosome breaks and common fragile site expression with the activation of ATM-mediated DNA damage checkpoint signaling
malfunction
DNA polymerase eta-deficient cells show strong activation of downstream DNA damage responses including ataxia-telangiectasia mutated and Rad3-related protein signaling and accumulate strand breaks as result of replication fork collapse
malfunction
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mutations in or altered expression of Pol gamma coupled with oxidative damage to mitochondrial DNA may be involved in Parkinson disease and Alzheimer disease
malfunction
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Pol beta-deficient spermatocytes are defective in meiotic chromosome synapsis and undergo apoptosis during prophase I, Pol beta-deficient seminferous tubules have few germ cells, Pol beta-deficient spermatocytes do not progress through meiosis, Pol beta-deficient mice are fertile
malfunction
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the depletion of Pol eta or Pol kappa elevates DNA damage associated with non-plasmid pULCtrl formed at the human c-MYC promoter
malfunction
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abolished catalytic activity of mutant enzyme in the presence of two metal ions, Mg2+ and Mn2+, overview
malfunction
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enhanced fidelity of base selection by a polymerase active site can result in impaired lesion bypass and delayed replication fork progression
malfunction
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more than 150 different point mutations in POLG, the gene encoding the human mitochondrial DNA polymerase gamma, cause a broad spectrum of childhood and adult onset diseases. Disorders associated with POLG mutations include: 1. myocerebrohepatopathy spectrum disorder 2. Alpers syndrome 3. ataxia neuropathy spectrum disorder 4. myoclonus epilepsy myopathy sensory ataxia 5. autosomal recessive progressive external ophthalmoplegia 6. autosomal dominant progressive external ophthalmoplegia. Also, alteration of the (CAG)10 repeat in the 2nd exon of POLG is implicated in male infertility
malfunction
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silencing of each polymerase, of mitochondrial DNA polymerases IB, IC, and ID, is lethal, resulting in kDNA loss, persistence of prereplication DNA monomers, and collapse of the mitochondrial membrane potential. Kinetics of kDNA loss during DNA polymerase silencing, overview
malfunction
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weakened Fe-S cluster binding efficiency of CysA mutant proteins, caused by a lack of polymerase complex stabilization by Pol31, even though this subunit interacts primarily with the CysB region, overexpression of Pol31 results in a 4 to 8fold higher 55Fe binding to both wild-type and CysA mutant Pol3-CTDs. Depletion of the cysteine desulfurase Nfs1 by growth on glucose of the galactose-regulatable strain Gal-NFS1 almost completely abolishes Fe binding to the polymerases, and depletion of the CIA machinery components Nbp35 and Nar1 in regulatable yeast strains abrogates Fe-S cluster formation on the polymerases
malfunction
many cancer-associated single-nucleotide polymorphisms have been reported in the Pol kappa gene, some of which are associated with poor survival and altered chemotherapy response
malfunction
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weakened Fe-S cluster binding efficiency of CysA mutant proteins, caused by a lack of polymerase complex stabilization by Pol31, even though this subunit interacts primarily with the CysB region, overexpression of Pol31 results in a 4 to 8fold higher 55Fe binding to both wild-type and CysA mutant Pol3-CTDs. Depletion of the cysteine desulfurase Nfs1 by growth on glucose of the galactose-regulatable strain Gal-NFS1 almost completely abolishes Fe binding to the polymerases, and depletion of the CIA machinery components Nbp35 and Nar1 in regulatable yeast strains abrogates Fe-S cluster formation on the polymerases
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metabolism
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high levels of DNA polymerases of the X family might cause genomic instability
metabolism
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the pol gamma holoenzyme functions in conjunction with the mitochondrial DNA helicase and the mitochondrial SSB to form the minimal replication apparatus
metabolism
DNA replication can be accomplished using dNDPs as substrates. In thermophiles, genome replication may be less sensitive to the energy charge of the cell than in mesophiles because thermostable polymerases can accept the diphosphorylated as well as the triphosphorylated substrates. DNA replication is thus less affected by the intracellular ATP/ADP ratio, and the relatively high efficiency with which DNA is synthesized at elevated temperatures suggests that thermophiles may be able to dispense with the triphosphorylated substrates entirely
metabolism
DNA replication can be accomplished using dNDPs as substrates. In thermophiles, genome replication may be less sensitive to the energy charge of the cell than in mesophiles because thermostable polymerases can accept the diphosphorylated as well as the triphosphorylated substrates. DNA replication is thus less affected by the intracellular ATP/ADP ratio, and the relatively high efficiency with which DNA is synthesized at elevated temperatures suggests that thermophiles may be able to dispense with the triphosphorylated substrates entirely
metabolism
DNA replication can be accomplished using dNDPs as substrates. In thermophiles, genome replication may be less sensitive to the energy charge of the cell than in mesophiles because thermostable polymerases can accept the diphosphorylated as well as the triphosphorylated substrates. DNA replication is thus less affected by the intracellular ATP/ADP ratio, and the relatively high efficiency with which DNA is synthesized at elevated temperatures suggests that thermophiles may be able to dispense with the triphosphorylated substrates entirely
metabolism
DNA replication can be accomplished using dNDPs as substrates. In thermophiles, genome replication may be less sensitive to the energy charge of the cell than in mesophiles because thermostable polymerases can accept the diphosphorylated as well as the triphosphorylated substrates. DNA replication is thus less affected by the intracellular ATP/ADP ratio, and the relatively high efficiency with which DNA is synthesized at elevated temperatures suggests that thermophiles may be able to dispense with the triphosphorylated substrates entirely
physiological function
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ABO4/POL2a/TIL1 is involved in DNA repair
physiological function
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both Pol eta and Pol kappa prevent genomic instability occurring at natural DNA sequences capable of forming unusual secondary structures in human cells
physiological function
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DNA polymerase beta is critical for mouse meiotic synapsis, Pol beta is required at a very early step in the processing of meiotic double-strand breaks, at or before the removal of SPO11 from double-strand break ends and the generation of the 3' single-stranded tails necessary for subsequent strand exchange
physiological function
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DNA polymerase epsilon and the histone H3 acetylase, Rtt109, are required for the formation/maintenance of this histone-depleted region and for the recruitment of the transcription factors to the tRNA
physiological function
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DNA polymerase epsilon with 3'-5' proofreading exonuclease activity bypasses only the model abasic site during processive synthesis and cannot reinitiate DNA synthesis
physiological function
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DNA polymerase eta confers UV resistance by catalyzing translesion synthesis past UV photoproducts
physiological function
DNA polymerase eta is a key protein in translesion synthesis in human cells, it is a low-fidelity enzyme when copying undamaged DNA but can carry out error-free translesion synthesis at sites of UV-induced dithymine cyclobutane pyrimidine dimmers. DNA polymerase eta plays an important role in preventing genome instability after UV- and cisplatin-induced DNA damage
physiological function
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DNA polymerase eta is a limiting factor for A:T mutations in immunglobulin genes and contributes to antibody affinity maturation in germinal center B cells
physiological function
DNA polymerase iota is also capable of error-free nucleotide incorporation opposite the bulky major groove adduct N-(deoxyguanosin-8-yl)-2-acetyl-aminofluorene
physiological function
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DNA polymerases have abortive DNA synthesis upon encountering apurinic/apyrimidinic sites. Under running start conditions, polB can incorporate in front of the damage and even replicate to the full-length oligonucleotides containing a specific apurinic/apyrimidinic site, but only when present at a molar excess. Conversely, bypassing activity of polD is strictly inhibited
physiological function
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human DNA polymerase eta modulates susceptibility to skin cancer by promoting translesion DNA synthesis past sunlight-induced cyclobutane pyrimidine dimers
physiological function
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human poliota protects cells from oxidative damage, poliota binds to chromatin after oxidative damage
physiological function
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involvement of deinococcal polymerase X in DNA-damage tolerance, possibly by contributing to DNA double-strand break repair and base excision repair
physiological function
Salasvirus phi29
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phi29 DNA polymerase is fully responsible for viral DNA replication
physiological function
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Pol alpha catalyses initiation of chromosomal DNA replication at origins and at Okazaki fragments on the lagging strand, Pol beta participates in base-excision repair, Pol gamma catalyses mitochondrial DNA synthetic processes, Pol delta participates in lagging-strand synthesis, and Pol epsilon has a role in the synthesis of the leading strand of chromosomal DNA, Pol eta functions in bypass UV lesions,Pol iota, Pol kappa, and Pol zeta function in bypass synthesis, Pol lambda functions in base excision repair, Pol mu functions in non-homologous end joining, Pol theta functions in DNA repair, and DNA polymerase Rec1 incorporates dC opposite abasic sites. Pol beta can be classified as a tumour suppressor
physiological function
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Pol beta is a DNA polymerase specific to base excision repair that also possesses lyase activity capable of severing the phosphoester bond on the 3' carbon of the abasic ribose
physiological function
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pol theta has no major involvement in somatic hypermutation
physiological function
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POLD4 is required for the in vitro pol delta activity, and functions in cell proliferation and maintenance of genomic stability of human cells
physiological function
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Poleta may be involved in induction of various types of mutations through the erroneous and efficient incorporation of oxidized dNTPs into DNA
physiological function
poliota uniquely replicates DNA with a constrained active site, creating shorter C1'-C1' strand distances, with the finger domain projecting the template base out towards the solvent-accessible major groove and stabilizing a mismatched G base through H-bonding
physiological function
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Polkappa efficiently bypasses 8-oxoguanine lesions, Polkappa increases Trypanosoma cruzi resistance to high doses of gamma irradiation and zeocin and can catalyse DNA synthesis within recombination intermediates
physiological function
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polymerase alpha (p70-p180 or p49-p58-p70-p180 complex) extends herpes primase-synthesized RNA primers much more efficiently than herpes polymerase
physiological function
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the interaction between DNA polymerase eta and MLH1 is involved in DNA replication, MutSalpha can interact with Poleta through MutLalpha
physiological function
the presence of 5'->3' exonuclease activity in DNA polymerase can replace mismatched base pairs with the correct nucleotide, DNA polymerase possesses 3'->5' exonuclease activity
physiological function
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Trypanosoma cruzi overexpressing Poleta is more resistant to treatment with hydrogen peroxide compared to nontransfected cells, does not increase its resistance to UV-light (with or without caffeine) or cisplatin, and is also unable to restore growth after treatment with zeocin or gamma irradiation
physiological function
Dbh DNA polymerase has multiple functions affecting the stability of the Sulfolobus genome, suppressing certain mutations at particular sites and promoting other mutations elsewhere
physiological function
Dpo3 is a potential player in the proper maintenance of the archaeal genome
physiological function
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3'-> 5'-exonucleolytic proofreading activity
physiological function
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DNA Pol lambda has a backup role for DNA Pol beta in base-excision repair
physiological function
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DNA polymerase beta from Trypanosoma cruzi is involved in kinetoplast DNA replication and repair of oxidative lesions, Tcpolbeta is involved in oxidative stress response, Tcpolbeta overexpression improves epimastigote survival in presence of H2O2
physiological function
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DNA polymerase III, an enzyme complex consisting of ten subunits, is responsible for genome duplication
physiological function
error-prone DNA polymerases belonging to the Y-family in mycobacteria do not participate in adaptive mutagenesis, in contrast to the representatives of theis faamily in other prokaryotes. Escherichia coli gene dinB homologues in mycobacteria code for nonfunctional molecules that are devoid of enzyme activity
physiological function
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most damage-induced mutagenesis in Escherichia coli is dependent on pol V Pol V has intrinsically weak DNA polymerase activity, but its catalytic activity can be stimulated in vitro in the presence the beta-processivity clamp, RecA protein bound to ssDNA, and single-stranded-binding (SSB) protein. Processivity of pol V in the presence of accessory factors, overview
physiological function
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pol gamma is absolutely essential for mitochondrial DNA replication and repair
physiological function
replicative DNA polymerase
physiological function
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the DNA polymerase catalyzes efficient and accurate translesion synthesis past cis-syn cyclobutane pyrimidine dimers, as well as 7,8-dihydro-8-oxoguanine and isomers of thymine glycol induced by reactive oxygen species
physiological function
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the enzyme plays an essential role in DNA replication, repair, and recombination
physiological function
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the parasite's single mitochondrion contains a unique catenated mitochondrial DNA network called kinetoplast DNA (kDNA) that is composed of minicircles and maxicircles. Three kDNA replication proteins (mitochondrial DNA polymerases IB, IC, and ID) are required for bloodstream form parasite viability
physiological function
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three eukaryotic DNA replicative polymerases, Pol alpha, Pol delta, and Pol epsilon, are involved in chromosomal DNA replication. RNA/DNA primers synthesized by Pol alpha/primase are elongated by Pol delta and/or Pol epsilon. Pol delta requires the DNA sliding clamp, proliferating cell nuclear antigen, PCNA, for highly processive enzyme activity
physiological function
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DNA damage that eludes cellular repair pathways can arrest the replication machinery and stall the cell cycle. This damage can be bypassed by the Y-family DNA polymerases
physiological function
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the Y-family DNA polymerases promote mutagenesis through the erroneous incorporation of oxidized dNTPs during DNA synthesis
physiological function
DNA polymerase epsilon (Pole) is responsible for leading strand synthesis. The presence of the C-terminal domain of the catalytic subunit (p261C) and the three small subunits regulates the 3'->5' exonuclease activity of the hPole holoenzyme. Together, the 3'->5 exonuclease activity and the variable mismatch extension activity modulate the overall fidelity of the hPole holoenzyme by up to 3 orders of magnitude. The presence of p261C and the three noncatalytic subunits optimizes the dual enzymatic activities of the catalytic p261 subunit and makes the hPole holoenzyme an efficient and faithful replicative DNA polymerase
physiological function
DNA polymerase eta plays a vital role in protection against skin cancer caused by damage from ultraviolet light. The enzyme rescues stalled replication forks at cyclobutane thymine-thymine dimers (TTDs) by inserting nucleotides opposite these DNA lesions
physiological function
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in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
physiological function
the enzyme has roles both in maintaining and compromising genomic integrity. The expression of pol kappa is altered in several different cancer types, which can lead to genome instability
physiological function
the enzyme is involved in repairing damaged DNA
physiological function
the template-dependent polymerase that can repair non-complementary DNA double strand breaks with unpaired 3' primer termini by nonhomologous end joining. Its role is to fill short gaps arising as intermediates in the process of V(D)J recombination and during processing of accidental double strand breaks
physiological function
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the Y-family DNA polymerases promote mutagenesis through the erroneous incorporation of oxidized dNTPs during DNA synthesis
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physiological function
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Dpo3 is a potential player in the proper maintenance of the archaeal genome
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physiological function
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the Y-family DNA polymerases promote mutagenesis through the erroneous incorporation of oxidized dNTPs during DNA synthesis
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physiological function
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involvement of deinococcal polymerase X in DNA-damage tolerance, possibly by contributing to DNA double-strand break repair and base excision repair
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physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
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physiological function
-
in translesion synthesis (TLS), specialized DNA polymerases, such as polymerase (pol) eta, are recruited to stalled replication forks. The polymerase form a multi-protein complex with PCNA, Rad6-Rad18, and other specialized polymerases. Pol eta interacts with PCNA and Rev1 via a PCNA-interacting protein (PIP) motif in its C-terminal unstructured region. PIP1 likely plays a critical role in the recruiting pol eta to the multi-protein complex. PIP2 likely plays a critical role in maintaining the architecture and the dynamics of this multi-protein complex needed to maximize the efficiency and accuracy of translesion synthesis
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additional information
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binding and recognition of the correct dNTP, the recombinant enzyme performs several small steps like local conformational changes involving active site residues, reorganization of Mg2+-coordinating ligands, and proton transfer
additional information
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nine residues, Tyr326, Leu329, Gln384, Lys387, Phe388, Met408, Asn422, Tyr438, and Phe451, are predicted to be involved in DNA/RNA distinction
additional information
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physiological importance of the two different metal cofactors, the [4Fe-4S] cluster in CysB and Zn2+ in CysA, in the stabilization of DNA polymerase interactions with different accessory proteins essential for processive DNA synthesis at the replication fork. CysA is an important determinant for proliferating cell nuclear antigen binding
additional information
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replicative DNA polymerases use a complex, multistep mechanism for efficient and accurate DNA replication, kinetics and conformational dynamics by single-molecule Förster resonance energy transfer techniques, overview. The replicative polymerase can bind to DNA in at least three conformations, corresponding to an open and closed conformation of the finger domain as well as a conformation with the DNA substrate bound to the exonuclease active site of PolB1. PolB1 can transition between these conformations without dissociating from a primer-template DNA substrate. The closed conformation is promoted by a matched incoming dNTP but not by a mismatched dNTP and that mismatches at the primer-template terminus lead to an increase in the binding of the DNA to the exonuclease site
additional information
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structural, kinetic and thermodynamic basis for the extraordinary accuracy of high-fidelity DNA polymerases, overview. The changes in enzyme structure following nucleotide binding govern the fate of the bound nucleotide, and the conformational change plays an essential role in establishing enzyme selectivity, conformational coupling between enzyme structure and fidelity, modeling of the universal mechanism: while the correct substrate induces a structure to facilitate catalysis, the wrong substrate induces a structure to slow catalysis and promote substrate release. Two-step sequence for nucleotide binding, two metal ion mechanism, nucleotide binds to the enzyme as an Mg-dNTP-2 complex, overview
additional information
structure modeling of K4 polymerase, overview
additional information
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the DNA polymerase V is comprised by the UmuD'2C protein complex. Pol V activity depends on the beta-clamp and gamma-clamp loaders UmuC and UmuD'2, overview
additional information
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the enzyme contains domains for binding ubiquitin and proliferating cell nuclear antigen
additional information
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the error frequency of the enzyme does not change significantly when the temperature is raised from 22°C to 72°C
additional information
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the holoenzyme of pol gamma consists of a catalytic subunit and a dimeric form of its accessory subunit, interaction of the accessory subunit with the pol gamma catalytic subunit enhances the processivity bx 50fold and the DNA binding properties of the catalytic subunit. The catalytic subunit is a 140 kDa enzyme, i.e. p140, that contains an N-terminal exonuclease domain connected by a linker region to a C-terminal polymerase domain and has DNA polymerase, 3'->5' exonuclease and 5' dRP lyase activities. The accessory subunit is a 55 kDa protein, i.e. p55, required for tight DNA binding and processive DNA synthesis
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the incorporation of 8-oxo-dGTP and 3'-azido-3'-deoxythymidine 5'-triphosphate by the human mitochondrial DNA polymerase provides an exception to the general rule that diphosphate release is fast. Analysis of the burst kinetics during incorporation of 8-oxo-dGTP shows that the amplitude of the burst is dependent upon the nucleotide concentration, diphosphate release is extremely slow following the incorporation of 3'-azido-3'-deoxythymidine 5'-triphosphate. The reversible chemistry and slow release of diphosphate decreases the specificity constant for the incorporation of 3'-azido-3'-deoxythymidine 5'-triphosphate and 8-oxo-dGTP. Brownian ratchet model, overview
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three aspartic acid residues D378, D380 and D531 form the catalytic carboxylate triad in pol E. Amino acid residues D378 and D531 are mainly responsible for the binding of metal chelated substrate dNTP, while D380 is solely responsible for the chemical step of phosphodiester bond formation
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nine residues, Tyr326, Leu329, Gln384, Lys387, Phe388, Met408, Asn422, Tyr438, and Phe451, are predicted to be involved in DNA/RNA distinction
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structure modeling of K4 polymerase, overview
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physiological importance of the two different metal cofactors, the [4Fe-4S] cluster in CysB and Zn2+ in CysA, in the stabilization of DNA polymerase interactions with different accessory proteins essential for processive DNA synthesis at the replication fork. CysA is an important determinant for proliferating cell nuclear antigen binding
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