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]

"dinB" redirects here. For the kind of bank, see deposit insurance national bank.
DNA pol IV
Identifiers
OrganismEscherichia coli
(str. K-12 substr. MG1655)
SymboldinB
Alt. symbolsdinP
Entrez944922
RefSeq (Prot)NP_414766.1
UniProtQ47155
Other data
EC number2.7.7.7
Chromosomegenome: 0.25 - 0.25 Mb
Search for
StructuresSwiss-model
DomainsInterPro

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
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
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