4q44
Polymerase-Damaged DNA Complex
Structural highlights
FunctionDPO4_ECOLI Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. Overexpression of polIV results in increased frameshift mutagenesis. It is required for stationary-phase adaptive mutation, which provides the bacterium with flexibility in dealing with environmental stress, enhancing long-term survival and evolutionary fitness. May be involved in translesional synthesis, in conjunction with the beta clamp from PolIII.[1] [2] [3] [4] [5] Publication Abstract from PubMedThe reduction in the efficacy of therapeutic antibiotics represents a global problem of increasing intensity and concern. Nitrofuran antibiotics act primarily through the formation of covalent adducts at the N(2) atom of the deoxyguanosine nucleotide in genomic DNA. These adducts inhibit replicative DNA polymerases (dPols), leading to the death of the prokaryote. N(2)-furfuryl-deoxyguanosine (fdG) represents a stable structural analog of the nitrofuran-induced adducts. Unlike other known dPols, DNA polymerase IV (PolIV) from E. coli can bypass the fdG adduct accurately with high catalytic efficiency. This property of PolIV is central to its role in reducing the sensitivity of E. coli toward nitrofuran antibiotics such as nitrofurazone (NFZ). We present the mechanism used by PolIV to bypass NFZ-induced adducts and thus improve viability of E. coli in the presence of NFZ. Our results can be used to develop specific inhibitors of PolIV that may potentiate the activity of nitrofuran antibiotics. Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic.,Kottur J, Sharma A, Gore KR, Narayanan N, Samanta B, Pradeepkumar PI, Nair DT Structure. 2015 Jan 6;23(1):56-67. doi: 10.1016/j.str.2014.10.019. Epub 2014 Dec , 11. PMID:25497730[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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