DNA polymerase IV

DNA polymerase IV is a prokaryotic polymerase that is involved in mutagenesis and is encoded by the dinB gene. It exhibits no 3′→5′ exonuclease (proofreading) activity and hence is error prone. In E. coli, DNA polymerase IV (Pol 4) is involved in non-targeted mutagenesis. 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 lesions via the appropriate repair pathway. 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 damaging agents.^[1]^[2]^[3]^[4]^[5]

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Replication bypass of 8-oxoguanine

Reactive oxygen species are produced continuously during normal metabolism and these damage DNA. DNA polymerase IV can catalyze translesion synthesis across a variety of DNA damages including 8-oxoguanine, a major oxidative damage with high mutagenic potential.^[6] Upon chromosome duplication by replicative polymerases, unrepaired 8-oxoguanine tends to mispair with A, so that during the next round of replication a G:C to T:A transversion mutation is produced (G:C → 8-oxoG:C → 8-oxoG:A → T:A). However, when DNA polymerase IV intervenes to bypass the damage, it preferentially incorporates the correct nucleotide CTP opposite 8-oxoguanine with high efficiency, thus avoiding potential mutations (G:C → 8-oxoG:C → 8-oxoG:C → GC).^[6]

References

^ Kim SR, Maenhaut-Michel G, Yamada M, Yamamoto Y, Matsui K, Sofuni T, Nohmi T, Ohmori H (December 1997). "Multiple pathways for SOS-induced mutagenesis in Escherichia coli: an overexpression of dinB/dinP results in strongly enhancing mutagenesis in the absence of any exogenous treatment to damage DNA". Proc. Natl. Acad. Sci. U.S.A. 94 (25): 13792–7. doi:10.1073/pnas.94.25.13792. PMC 28386. PMID 9391106.
^ Napolitano R, Janel-Bintz R, Wagner J, Fuchs RP (November 2000). "All three SOS-inducible DNA polymerases (Pol II, Pol IV and Pol V) are involved in induced mutagenesis". EMBO J. 19 (22): 6259–65. doi:10.1093/emboj/19.22.6259. PMC 305832. PMID 11080171.
^ McKenzie GJ, Lee PL, Lombardo MJ, Hastings PJ, Rosenberg SM (March 2001). "SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification". Mol. Cell. 7 (3): 571–9. doi:10.1016/s1097-2765(01)00204-0. PMID 11463382.
^ Lenne-Samuel N, Wagner J, Etienne H, Fuchs RP (January 2002). "The processivity factor beta controls DNA polymerase IV traffic during spontaneous mutagenesis and translesion synthesis in vivo". EMBO Rep. 3 (1): 45–9. doi:10.1093/embo-reports/kvf007. PMC 1083926. PMID 11751576.
^ Yeiser B, Pepper ED, Goodman MF, Finkel SE (June 2002). "SOS-induced DNA polymerases enhance long-term survival and evolutionary fitness". Proc. Natl. Acad. Sci. U.S.A. 99 (13): 8737–41. doi:10.1073/pnas.092269199. PMC 124368. PMID 12060704.
^ ^a ^b Raper AT, Gadkari VV, Maxwell BA, Suo Z (2016). "Single-Molecule Investigation of Response to Oxidative DNA Damage by a Y-Family DNA Polymerase". Biochemistry. 55 (14): 2187–96. doi:10.1021/acs.biochem.6b00166. PMC 5026495. PMID 27002236.

DNA replication (comparing prokaryotic to eukaryotic)

Initiation

Prokaryotic (initiation)	Pre-replication complex dnaC 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 polymerase III holoenzyme dnaC dnaE dnaH dnaN dnaQ dnaT dnaX holA holB holC holD holE Replisome DNA ligase DNA clamp Topoisomerase DNA gyrase Prokaryotic DNA polymerase: DNA polymerase I Klenow fragment
Eukaryotic (synthesis in S phase)	Replication factor C RFC1 Flap endonuclease FEN1 Topoisomerase Replication protein A RPA1 Eukaryotic DNA polymerase: alpha POLA1 POLA2 PRIM1 PRIM2 delta POLD1 POLD2 POLD3 POLD4 epsilon POLE POLE2 POLE3 POLE4 DNA clamp PCNA Control of chromosome duplication
Both	Movement: Processivity DNA ligase

Termination

Telomere: Telomerase
- TERT
- TERC
- DKC1

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)

2.7.7: nucleotidyltransferase
(PO₄-nucleoside)

Polymerase

DNA polymerase	DNA-directed DNA polymerase I/A γ θ ν T7 Taq II/B α δ ε ζ Pfu III/C IV/X β λ μ TDT V/Y η ι κ RNA-directed DNA polymerase Reverse transcriptase Telomerase
RNA polymerase	Template-directed RNA polymerase I II III IV V ssRNAP POLRMT Primase 1 2 PrimPol RNA-dependent RNA polymerase Polyadenylation PAP PNPase

Phosphorolytic
3' to 5' exoribonuclease

Nucleotidyltransferase

Guanylyltransferase

mRNA capping enzyme

Other

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 promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	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) EC7 Translocases (list)

This page was last edited on 13 March 2023, at 03:25

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Transcription

Replication bypass of 8-oxoguanine

References