Information on EC 2.7.7.7 - DNA-directed DNA polymerase and Organism(s) Homo sapiens

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Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.7.7
-
RECOMMENDED NAME
GeneOntology No.
DNA-directed DNA polymerase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
a 2'-deoxyribonucleoside 5'-triphosphate + DNAn = diphosphate + DNAn+1
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nucleotidyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Purine metabolism
-
-
Pyrimidine metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase (DNA-directed)
Catalyses DNA-template-directed extension of the 3'- end of a DNA strand by one nucleotide at a time. Cannot initiate a chain de novo. Requires a primer, which may be DNA or RNA. See also EC 2.7.7.49 RNA-directed DNA polymerase.
CAS REGISTRY NUMBER
COMMENTARY hide
9012-90-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-hydroxy-2'-deoxyadenosine 5'-triphosphate + DNAn
diphosphate + DNAn+1
show the reaction diagram
-
DNA polymerase eta incorporates 2-hydroxy-2'-deoxyadenosine 5'-triphosphate opposite template G during DNA synthesis
-
-
?
8-hydroxy-2'-deoxyguanosine 5'-triphosphate + DNAn
diphosphate + DNAn+1
show the reaction diagram
-
DNA polymerase eta incorporates 8-hydroxy-2'-deoxyguanosine 5'-triphosphate opposite template A and slightly opposite template C during DNA synthesis
-
-
?
dATP + DNAn
diphosphate + DNAn+1
show the reaction diagram
-
with activated calf thymus DNA
-
-
?
dCTP + DNAn
diphosphate + DNAn+1
show the reaction diagram
deoxynucleoside triphosphate + DNAn
diphosphate + DNAn+1
show the reaction diagram
dGTP + DNAn
diphosphate + DNAn+1
show the reaction diagram
-
with activated calf thymus DNA
-
-
?
dTTP + DNAn
diphosphate + DNAn+1
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
deoxynucleoside triphosphate + DNAn
diphosphate + DNAn+1
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Na+
-
pols beta, iota and zeta exhibit maximal activity under conditions of moderate NaCl concentrations of 20-60 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2E)-2-(3-nitro-4-[[6-(trifluoromethyl)pyridin-3-yl]sulfanyl]benzylidene)-5-thioxo-1,3-thiazolidin-4-one
-
-
(2E)-2-(4-chloro-3-ethylbenzylidene)-5-thioxo-1,3-thiazolidin-4-one
-
-
(2E)-2-(pentafluorobenzylidene)-5-thioxodihydrothiophen-3(2H)-one
-
-
(2E)-2-[4-(2-hydroxyethyl)-3-nitrobenzylidene]-5-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-(4-chloro-3-nitrobenzylidene)-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[3-bromo-4-[(4-fluorobenzyl)oxy]benzylidene]-1,3-thiazolidine-2,4-dione
-
-
(5Z)-5-[3-bromo-4-[(4-fluorophenyl)sulfanyl]benzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[3-nitro-4-(pyridin-3-ylsulfanyl)benzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[4-(4-methylphenoxy)-3-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[4-(cyclohexylsulfanyl)-3-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[4-[(4-bromophenyl)sulfanyl]-3-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[4-[(4-chlorophenyl)sulfanyl]-3-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[4-[(4-fluorobenzyl)oxy]-3-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[4-[(4-fluorobenzyl)oxy]benzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
(5Z)-5-[4-[(4-methylphenyl)sulfanyl]-3-nitrobenzylidene]-3-(prop-2-en-1-yl)-2-thioxo-1,3-thiazolidin-4-one
-
-
(9-adenylmethylcarbonyl)-4-aminobutyl triphosphate
-
fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A
(biphenylcarbonyl)-4-oxobutyl triphosphate
-
fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A; inhibits wild-type enzyme and mutant enzyme Y505A
(E)-enedione
-
-
1,2,3,4-tetrahydro-5-methoxynaphthalene-1,4-diol
-
i.e. nodulisporol. Strong inhibition of pol lambda, but does not influence the activities of mammalian pols alpha to kappa, and shows no effect on the activities of plant pols alpha and beta, prokaryotic pols, and other DNA metabolic enzymes such as calf terminal deoxynucleotidyl transferase, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, and bovine deoxyribonuclease I
1,3-bis[2-chloroethyl]-2-nitrosourea
-
-
1-deoxyrubralactone
-
potent inhibitor of isozymes pol kappa, pol lambda, pol iota, and pol eta, but does not inhibit DNA polymerase isozymes pol delta, pol epsilon, and pol gamma
10-epi-pyragonicin
-
-
19-epi-jimenezin
-
-
2',3'-dideoxy-ATP
-
poor inhibitor
2-(p-n-Butylanilino)-2'-deoxyadenosine 5'-triphosphate
2-butylanilino-dATP
-
potent and highly selective inhibitor
2-methoxy-4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl 2,4-dichlorobenzoate
-
-
2-methoxy-4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl 3-bromobenzoate
-
-
2-thiomethyl-6-phenyl-4-(4'-hydroxybutyl)-1,2,4,-triazole (5,1-C)(1,2,4)triazine-7-one triphosphate
-
fully competitive with respect to the nucleotide substrate dTTP; fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A
3,4-dihydro-4-hydroxy-8-methoxynaphthalen-1(2H)-one
-
i.e. nodulisporone. Strong inhibition of pol lambda, but does not influence the activities of mammalian pols alpha to kappa, and shows no effect on the activities of plant pols alpha and beta, prokaryotic pols, and other DNA metabolic enzymes such as calf terminal deoxynucleotidyl transferase, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, and bovine deoxyribonuclease I
3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin
-
-
4-chloromercuribenzoic acid
-
-
4-chlorophenyl 2,4-dinitrophenyl sulfide
-
-
4-hydroxy-5-methyl-3-tetradecyl-dihydrofuran-2(3H)-one
-
-
4-[(4-methylphenyl)sulfanyl]-3-nitrobenzaldehyde
-
-
4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-2-methoxyphenyl 3-bromobenzoate
-
-
4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl 2-chlorobenzoate
-
-
5-(5-nitro-2-[[6-(trifluoromethyl)pyridin-3-yl]sulfanyl]benzylidene)-2-thioxo-1,3-thiazolidin-4-one
-
-
5-[2-(cyclohexylsulfanyl)-5-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
5-[2-[(4-chlorophenyl)sulfanyl]-5-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
5-[2-[(4-methylphenyl)sulfanyl]-5-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
-
-
adefovir diphosphate
-
-
Allicin
-
-
alliin
-
-
aphidicolin
Ara-ATP
-
-
aurintricarboxylic acid
-
potent nanomolar inhibitor of pol beta, pol iota, and pol zeta
Ca2+
-
polymerase alpha
Carbonyldiphosphonate
cholesterol hemisuccinate
-
pol beta; pol iota; pol kappa; pol lambda
cloretazine
-
i.e. 1,2-bis[methylsulfonyl]-1-[2-chloroethyl]-2-[(methylamino)carbonyl]hydrazine
diallyl pentasulfide
-
-
diallyl tetrasulfide
-
-
diallyl trisulfide
-
-
Dideoxynucleoside 5'-triphosphate
Dideoxythymidine triphosphate
dimethyl sulfoxide
-
stimulates DNA polymerase alpha and delta, inhibits human DNA polymerase epsilon
ellagic acid
-
potent nanomolar inhibitor of pol beta, pol iota, and pol zeta
epigallocatechin gallate
-
-
gemcitabine
-
i.e. 2'-deoxy-2',2'-difluorocytidine, when gemcitabine is encountered as a template base DNA polymerase gamma pauses at the lesion and one downstream position but eventually elongates the primer to full-length product, these pauses are because of a 1000fold decrease in nucleotide incorporation efficiency
hymenoic acid
-
specific inhibitor of human DNA polymerase lambda, non-competitive inhibition with respect to both the DNA template-primer and the dNTP, i.e trans-4-[(1'E,5'S)-5'-carboxy-1'-methyl-1'-hexenyl]cyclohexanecarboxylic acid, does not influence the activities of the other mammalian pols alpha, gamma, delta, epsilon, eta, iota, and kappa, and also shows no effect even on the activity of pol beta
jimenezin
-
-
lamivudine triphosphate
-
-
Li+
-
polymerase alpha
Mg2+
-
DNA polymerase alpha: free Mg2+ competes with primer for enzyme binding, dramatic inhibition at Mg2+ concentration above the optimum
muconin
-
-
N-(2,4-dinitro-5-fluorophenyl)-2-aminoethyl triphosphate
-
inhibition of mutant enzyme Y505A, inactive against wild-type enzyme
N-(2,4-dinitro-5-fluorophenyl)-4-aminobutyl triphosphate
-
fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A
N-(2,4-dinitro-5-imidazolylphenyl)-2-aminoethyl triphosphate
-
inhibition of mutant enzyme Y505A, inactive against wild-type enzyme
N-(2,4-dinitro-5-imidazolylphenyl)-4-aminobutyl triphosphate
-
inhibition of mutant enzyme Y505A, inactive against wild-type enzyme
N-(2,4-dinitrophenyl)-4-aminobutyl triphosphate
-
fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A
N-(benzyloxycarbonyl)-4-aminobutyl triphosphate
-
fully competitive with respect to the nucleotide substrate dTTP, inhibits wild-type enzyme and mutant enzyme Y505A; inhibits wild-type enzyme and mutant enzyme Y505A
N-ethylmaleimide
N-[6-N-(2,4-dinitrophenyl)aminohexanoyl]-2-aminoethyl triphosphate
-
inhibition of mutant enzyme Y505A, inactive against wild-type enzyme
N2-(p-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate
-
inhibition of DNA polymerase alpha at 100fold; lower concentration than DNA polymerase delta
N2-CH2(6-benzo[a]pyrenyl)guanine
-
severely blocks activity
-
N2-CH2(9-anthracenyl)guanine
-
severely blocks activity, frequencies of dATP misinsertion and extension beyond mispairs are proportionally increased, great decrease in pre-steady-state kinetic burst rate. 2.6fold decrease in dCTP binding affinity and increased DNA substrate binding affinity
-
NSC-666715
-
potent, small molecular weight inhibitor of DNA polymerase beta, blocks Pol-beta-directed single-nucleotide- and long-patch-base excisison repair
Oosporein
-
50% inhibition at 0.61 mM
pamoic acid
-
pol beta inhibitor
plakevulin A
-
-
pyragonicin
-
-
pyranicin
-
potent inhibitor
rhodanines
-
most potent inhibitors for DNA Pol lambda, they are up to 10times less active against the highly similar DNA polymerase beta, structure-activity relationships, overview. 5-Arylidene-2,4-thiazolidinediones are class I rhodanines, rhodanine class II has members of carbohydrazides, and class III contains a common 2,4-pentadione substructure element
-
Salt
-
concentrations above 50 mM inhibit: human KB cell polymerase alpha
single-stranded DNA
-
inhibition of polymerase alpha, competitive with respect to activated DNA substrate
stavudine triphosphate
-
-
talaroflavone
-
-
tenofovir diphosphate
-
-
untenone A
-
-
vitamin K3
-
more than 80% inhibition of pol gamma at 0.03 mM, does not affect other human DNA polymerase isozymes
zidovudine triphosphate
-
-
[3-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy]acetic acid
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dimethyl sulfoxide
-
stimulates DNA polymerase alpha and delta, inhibits human DNA polymerase epsilon
FEN1
-
stimulates strand displacement activity, DEN1 processes nicked DNA, thus removing a barrier to Pol lambda DNA synthesis. It results in a one-nucleotide gapped DNA molecule that is a favorite substrate of Pol lambda
-
PCNA
-
stimulates strand displacement activity
-
Polymerase alpha accessory factors
-
overview
-
proliferating cell nuclear antigen
-
Replication factor A
-
RF-A, multisubunit single-stranded DNA-binding protein, functions as an auxiliary protein for both polymerases alpha and delta, required for initiation and elongation stages of in vitro SV40 DNA replication
-
Replication factor C
-
RF-C, multisubunit protein complex with primer/template binding and DNA-dependent ATPase activity, has a profound effect on leading-strand DNA synthesis
-
spermidine
-
up to 10 mM, polymerase beta
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00249 - 0.00792
dCTP
0.00118
deoxynucleoside triphosphate
-
DNA polymerase lambda, in 50 mM Tris-HCl (pH 7.5), 1 mM dithiothreitol, 50% (v/v) glycerol, and 0.1 mM EDTA, at 37°C
0.175 - 0.211
dTTP
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0028 - 0.0038
(9-adenylmethylcarbonyl)-4-aminobutyl triphosphate
0.0004 - 0.0048
(biphenylcarbonyl)-4-oxobutyl triphosphate
0.0188
2',3'-dideoxy-ATP
-
-
0.001
2-butylanilino-dATP
-
-
0.0018 - 0.068
2-thiomethyl-6-phenyl-4-(4'-hydroxybutyl)-1,2,4,-triazole (5,1-C)(1,2,4)triazine-7-one triphosphate
0.00271
adefovir diphosphate
-
-
0.00065
aphidicolin
-
-
0.0506
lamivudine triphosphate
-
-
0.0144
N-(2,4-dinitro-5-fluorophenyl)-2-aminoethyl triphosphate
-
mutant enzyme Y505A
0.0031 - 0.0065
N-(2,4-dinitro-5-fluorophenyl)-4-aminobutyl triphosphate
0.0005
N-(2,4-dinitro-5-imidazolylphenyl)-2-aminoethyl triphosphate
-
mutant enzyme Y505A
0.0154
N-(2,4-dinitro-5-imidazolylphenyl)-4-aminobutyl triphosphate
-
mutant enzyme Y505A
0.0012 - 0.0035
N-(2,4-dinitrophenyl)-4-aminobutyl triphosphate
0.0016 - 0.07
N-(benzyloxycarbonyl)-4-aminobutyl triphosphate
0.0091
N-[6-N-(2,4-dinitrophenyl)aminohexanoyl]-2-aminoethyl triphosphate
-
mutant enzyme Y505A
0.0569
stavudine triphosphate
-
-
0.00618
tenofovir diphosphate
-
-
additional information
additional information
-
Allium sativum extract has an KI value of 0.0112 mM using DNA polymerase lambda, in 50 mM Tris-HCl (pH 7.5), 1 mM dithiothreitol, 50% (v/v) glycerol, and 0.1 mM EDTA, at 37°C
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011 - 0.1
(2E)-2-(3-nitro-4-[[6-(trifluoromethyl)pyridin-3-yl]sulfanyl]benzylidene)-5-thioxo-1,3-thiazolidin-4-one
0.0083 - 0.08
(5Z)-5-[3-bromo-4-[(4-fluorophenyl)sulfanyl]benzylidene]-2-thioxo-1,3-thiazolidin-4-one
0.0093 - 0.1
(5Z)-5-[4-(4-methylphenoxy)-3-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
0.0059 - 0.0644
(5Z)-5-[4-[(4-fluorobenzyl)oxy]benzylidene]-2-thioxo-1,3-thiazolidin-4-one
0.0037 - 0.0088
(E)-enedione
0.092 - 0.307
1,2-bis[methylsulfonyl]-1-[(methylamino)carbonyl]hydrazine
0.271 - 1.435
1,3-bis[2-chloroethyl]-2-nitrosourea
0.0598
1-deoxyrubralactone
Homo sapiens
-
in 50 mM Tris-HCl (pH 7.5) containing 1 mM dithiothreitol, 50% (v/v) glycerol, and 0.1 mM EDTA, at 37°C
0.049
3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin
Homo sapiens
-
-
0.0124 - 0.0888
4-[(Z)-(4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]phenyl 2-chlorobenzoate
0.0081 - 0.0429
5-[2-[(4-chlorophenyl)sulfanyl]-5-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
0.01 - 0.0455
5-[2-[(4-methylphenyl)sulfanyl]-5-nitrobenzylidene]-2-thioxo-1,3-thiazolidin-4-one
0.0063 - 0.148
cholesterol hemisuccinate
0.074 - 0.387
cloretazine
0.146
diallyl trisulfide
Homo sapiens
-
DNA polymerase lambda, in 50 mM Tris-HCl (pH 7.5), 1 mM dithiothreitol, 50% (v/v) glycerol, and 0.1 mM EDTA, at 37°C
0.0038
epigallocatechin gallate
Homo sapiens
-
pH and temperature not specified in the publication
0.0917
hymenoic acid
Homo sapiens
-
-
0.0049 - 0.06
pamoic acid
0.066 - 0.179
plakevulin A
0.0023 - 0.0158
pyranicin
0.0043 - 0.057
untenone A
0.006
vitamin K3
Homo sapiens
-
isozyme pol gamma, in 50 mM Tris-HCl (pH 7.5) containing 1 mM dithiothreitol, 50% (v/v) glycerol, and 0.1 mM EDTA, at 37°C
additional information
additional information
Homo sapiens
-
Allium sativum extract has an IC50 of 0.0345 mM, using DNA polymerase lambda in 50 mM Tris-HCl (pH 7.5), 1 mM dithiothreitol, 50% (v/v) glycerol, and 0.1 mM EDTA, at 37°C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.968
-
polymerase beta
3.43
-
polymerase alpha
5.33
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 7.9
-
assay at
7.5 - 8.5
-
KB cell DNA polymerase alpha
8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2 - 9
-
pH 7.2: about 65% of maximal activity, pH 9.0: about 40% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5
-
polymerase alpha
5.6 - 5.9
-
polymerase C, sucrose gradient, ampholytes pH 3-11
8.5
-
polymerase beta
9.3
-
polymerase N1, sucrose gradient, ampholytes pH 3-11
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
human DNA polymerase eta expression is detected in most tissues except for very low or undetectable levels in peripheral lymphocytes, fetal spleen, and adult muscle
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT