scholarly journals Specificity of damage-bypass DNA polymerases E. coli DinB and human pol κ

2017 ◽  
Author(s):  
Antczak
Keyword(s):  
Dna Polymerases ◽  
E Coli

The Mechanism of Replication of Single-Stranded DNA. VI. Requirements for Ribonucleoside Triphosphates and DNA Polymerase III

1973 ◽  
Vol 51 (12) ◽  
pp. 1588-1597 ◽  
Author(s):  
David T. Denhardt ◽  
Makoto Iwaya ◽  
Grant McFadden ◽  
Gerald Schochetman
Keyword(s):  
Dna Polymerase ◽  
Dna Polymerases ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Dna Polymerase Iii ◽  
Single Stranded Dna ◽  
E Coli ◽  
Polymerase Iii

Evidence is presented that in Escherichia coli made permeable to nucleotides by exposure to toluene, the synthesis of a DNA chain complementary to the infecting single-stranded DNA of bacteriophage [Formula: see text] requires ATP as well as the four deoxyribonucleoside triphosphates. This synthesis results in the formation of the parental double-stranded replicative-form (RF) molecule. The ATP is not required simply to prevent degradation of the ribonucleoside or deoxyribonucleoside triphosphates; it can be partially substituted for by other ribonucleoside triphosphates.No single one of the known E. coli DNA polymerases appears to be uniquely responsible in vivo for the formation of the parental RF. Since [Formula: see text] replicates well in strains lacking all, or almost all, of the in-vitro activities of DNA polymerases I and II, neither of these two enzymes would seem essential; and in a temperature-sensitive E. coli mutant (dnaEts) deficient in DNA polmerase-I activity and possessing a temperature-sensitive DNA polymerase III, the viral single-stranded DNA is efficiently incorporated into an RF molecule at the restrictive temperature. In contrast, both RF replication and progeny single-stranded DNA synthesis are dependent upon DNA polymerase III activity.

Roles of E. coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis

Nature ◽  
2000 ◽  
Vol 404 (6781) ◽  
pp. 1014-1018 ◽  
Author(s):  
Mengjia Tang ◽  
Phuong Pham ◽  
Xuan Shen ◽  
John-Stephen Taylor ◽  
Mike O'Donnell ◽  
...  
Keyword(s):  
Dna Polymerases ◽  
E Coli ◽  
Sos Mutagenesis

Interaction of 5-Methoxymethyl-2′-Deoxyuridine Triphosphate with DNA Polymerases: Effects of the 5-Substituent and Comparison with the Deoxycytidine Derivative

1992 ◽  
Vol 3 (4) ◽  
pp. 243-247 ◽  
Author(s):  
P. J. Aduma ◽  
S. V. Gupta ◽  
A. L. Stuart
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Competitive Inhibitor ◽  
E Coli ◽  
The Difference ◽  
Simplex Virus ◽  
Selective Activity ◽  
Hsv 1

5-Methoxymethyl-2′-deoxyuridine (MMdUrd) is a selective anti-herpes agent that is dependent upon initial phosphorylation by Herpes simplex virus-induced deoxythymidine kinase. In order to determine its mechanism of action, MMdUrd was converted to the 5′-triphosphate (MMdUTP) and the nature of interaction of MMdUTP and dTTP with DNA polymerase of E. coli, HSV-1, and human α was investigated. The order of utilization of deoxyuridine analogues by bacterial and HSV-1 DNA polymerases for DNA synthesis was: dTTP > MMdUTP. In contrast, 5-methoxymethyl-2′-deoxycytidine-5′-triphosphate (MMdCTP) was a better substrate for HSV DNA polymerase compared to dCTP. MMdUTP is a competitive inhibitor of HSV-1 DNA polymerase with respect to dTTP incorporation (Ki = 2.9 × 10−6M). The IC50 values of MMdUTP for both HSV and human αDNA polymerases were 4.5 × 10 −6M. These data suggest that the selective activity of MMdUrd is due to its preferential phosphorylation by viral thymidine kinase and not at the DNA polymerase level. These results may also account for the difference in anti-HSV activity between MMdUrd and its deoxycytidine analogue.

scholarly journals Ada protein– and sequence context–dependent mutagenesis of alkyl phosphotriester lesions in Escherichia coli cells

2020 ◽  
Vol 295 (26) ◽  
pp. 8775-8783
Author(s):  
Jiabin Wu ◽  
Jun Yuan ◽  
Nathan E. Price ◽  
Yinsheng Wang
Keyword(s):  
Escherichia Coli ◽  
Dna Replication ◽  
Adaptive Response ◽  
Dna Polymerases ◽  
Replication Machinery ◽  
Sequence Context ◽  
E Coli ◽  
Highly Efficient ◽  
Escherichia Coli Cells ◽  
Ada Protein

Alkyl phosphotriester (alkyl-PTE) lesions are frequently induced in DNA and are resistant to repair. Here, we synthesized and characterized methyl (Me)- and n-butyl (nBu)-PTEs in two diastereomeric configurations (Sp and Rp) at six different flanking dinucleotide sites, i.e. XT and TX (X = A, C, or G), and assessed how these lesions impact DNA replication in Escherichia coli cells. When single-stranded vectors contained an Sp-Me-PTE in the sequence contexts of 5′-AT-3′, 5′-CT-3′, or 5′-GT-3′, DNA replication was highly efficient and the replication products for all three sequence contexts contained 85–90% AT and 5–10% TG. Thus, the replication outcome was largely independent of the identity of the 5′ nucleotide adjacent to an Sp-Me-PTE. Furthermore, replication across these lesions was not dependent on the activities of DNA polymerases II, IV, or V; Ada, a protein involved in adaptive response and repair of Sp-Me-PTE in E. coli, however, was essential for the generation of the mutagenic products. Additionally, the Rp diastereomer of Me-PTEs at XT sites and both diastereomers of Me-PTEs at TX sites exhibited error-free replication bypass. Moreover, Sp-nBu-PTEs at XT sites did not strongly impede DNA replication, and other nBu-PTEs displayed moderate blockage effects, with none of them being mutagenic. Taken together, these findings provide in-depth understanding of how alkyl-PTE lesions are recognized by the DNA replication machinery in prokaryotic cells and reveal that Ada contributes to mutagenesis of Sp-Me-PTEs in E. coli.

Mirror image stereoisomers of the major benzo[a]pyrene N2-dG adduct are bypassed by different lesion-bypass DNA polymerases in E. coli

DNA Repair ◽  
2006 ◽  
Vol 5 (4) ◽  
pp. 515-522 ◽  
Author(s):  
Kwang Young Seo ◽  
Arumugam Nagalingam ◽  
Shadi Miri ◽  
Jun Yin ◽  
Sushil Chandani ◽  
...  
Keyword(s):  
Dna Polymerases ◽  
Mirror Image ◽  
Lesion Bypass ◽  
E Coli

Effect of metal cations on misincorporation by E. coli DNA polymerases

1977 ◽  
Vol 77 (3) ◽  
pp. 854-860 ◽  
Author(s):  
Michiko Miyaki ◽  
Ikuko Murata ◽  
Michiko Osabe ◽  
Tetsuo Ono
Keyword(s):  
Dna Polymerases ◽  
Metal Cations ◽  
E Coli

scholarly journals The Roles of UmuD in Regulating Mutagenesis

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Jaylene N. Ollivierre ◽  
Jing Fang ◽  
Penny J. Beuning
Keyword(s):  
Dna Damage ◽  
Protein Interactions ◽  
Dna Polymerases ◽  
Gene Products ◽  
E Coli ◽  
Domains Of Life ◽  
Induced Mutagenesis ◽  
Multiple Conformations ◽  
Y Family ◽  
Damaged Dna

All organisms are subject to DNA damage from both endogenous and environmental sources. DNA damage that is not fully repaired can lead to mutations. Mutagenesis is now understood to be an active process, in part facilitated by lower-fidelity DNA polymerases that replicate DNA in an error-prone manner. Y-family DNA polymerases, found throughout all domains of life, are characterized by their lower fidelity on undamaged DNA and their specialized ability to copy damaged DNA. TwoE. coliY-family DNA polymerases are responsible for copying damaged DNA as well as for mutagenesis. These DNA polymerases interact with different forms of UmuD, a dynamic protein that regulates mutagenesis. The UmuD gene products, regulated by the SOS response, exist in two principal forms:UmuD2, which prevents mutagenesis, andUmuD2′, which facilitates UV-induced mutagenesis. This paper focuses on the multiple conformations of the UmuD gene products and how their protein interactions regulate mutagenesis.

scholarly journals MsDpo4—a DinB Homolog fromMycobacterium smegmatis—Is an Error-Prone DNA Polymerase That Can Promote G:T and T:G Mismatches

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Amit Sharma ◽  
Deepak T. Nair
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dna Polymerase ◽  
Environmental Conditions ◽  
Mycobacterium Smegmatis ◽  
Molecular Level ◽  
Dna Polymerases ◽  
Adaptive Mutagenesis ◽  
E Coli ◽  
Nucleotide Incorporation ◽  
Y Family

Error-prone DNA synthesis in prokaryotes imparts plasticity to the genome to allow for evolution in unfavorable environmental conditions, and this phenomenon is termed adaptive mutagenesis. At a molecular level, adaptive mutagenesis is mediated by upregulating the expression of specialized error-prone DNA polymerases that generally belong to the Y-family, such as the polypeptide product of thedinBgene in case ofE. coli. However, unlikeE. coli, it has been seen that expression of the homologs ofdinBinMycobacterium tuberculosisare not upregulated under conditions of stress. These studies suggest that DinB homologs inMycobacteriamight not be able to promote mismatches and participate in adaptive mutagenesis. We show that a representative homolog fromMycobacterium smegmatis(MsDpo4) can carry out template-dependent nucleotide incorporation and therefore is a DNA polymerase. In addition, it is seen that MsDpo4 is also capable of misincorporation with a significant ability to promote G:T and T:G mismatches. The frequency of misincorporation for these two mismatches is similar to that exhibited by archaeal and prokaryotic homologs. Overall, our data show that MsDpo4 has the capacity to facilitate transition mutations and can potentially impart plasticity to the genome.

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