The role of nucleotide excision repair of Escherichia coli in repair of spontaneous and gamma-radiation-induced DNA damage in the lacZα gene

Kuipers, Gitta K.; Slotman, Ben J.; Poldervaart, Hester A; Vilsteren, Ingrid M.J van; Reitsma-Wijker, Carola A; Lafleur, M.V.M.

doi:10.1016/s0921-8777(00)00021-5

Cited by 9 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The spontaneous mutation frequency of uvrA-deficient E. coli strains shows a significant reduction in T→C transitions (85), consistent with NER and gap fill-in by PolY1 at endogenously damaged DNA. NER may also play a role in removing misincorporated ribonucleotides from DNA, as has been observed in E. coli (86).…”

Section: Discussionsupporting

confidence: 52%

An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis

Million-Weaver¹,

Samadpour²,

Moreno-Habel³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

128

View full text Add to dashboard Cite

We previously reported that lagging-strand genes accumulate mutations faster than those encoded on the leading strand in Bacillus subtilis. Although we proposed that orientation-specific encounters between replication and transcription underlie this phenomenon, the mechanism leading to the increased mutagenesis of lagging-strand genes remained unknown. Here, we report that the transcription-dependent and orientation-specific differences in mutation rates of genes require the B. subtilis Y-family polymerase, PolY1 (yqjH). We find that without PolY1, association of the replicative helicase, DnaC, and the recombination protein, RecA, with lagging-strand genes increases in a transcription-dependent manner. These data suggest that PolY1 promotes efficient replisome progression through lagging-strand genes, thereby reducing potentially detrimental breaks and single-stranded DNA at these loci. Y-family polymerases can alleviate potential obstacles to replisome progression by facilitating DNA lesion bypass, extension of D-loops, or excision repair. We find that the nucleotide excision repair (NER) proteins UvrA, UvrB, and UvrC, but not RecA, are required for transcription-dependent asymmetry in mutation rates of genes in the two orientations. Furthermore, we find that the transcription-coupling repair factor Mfd functions in the same pathway as PolY1 and is also required for increased mutagenesis of laggingstrand genes. Experimental and SNP analyses of B. subtilis genomes show mutational footprints consistent with these findings. We propose that the interplay between replication and transcription increases lesion susceptibility of, specifically, lagging-strand genes, activating an Mfd-dependent error-prone NER mechanism. We propose that this process, at least partially, underlies the accelerated evolution of lagging-strand genes.replication conflicts | transcription orientation | Y-family polymerases | excision repair | TCR

show abstract

Section: Discussionsupporting

confidence: 52%

An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis

Million-Weaver¹,

Samadpour²,

Moreno-Habel³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

128

View full text Add to dashboard Cite

show abstract

“…1) although the opposite tendency was previously reported [50]. In addition, the introduction of the pSF11 plasmid carrying the uvrA gene into the uvrA strain increased the control mutant frequency (Table 2, Expt.…”

Section: Discussionmentioning

confidence: 63%

UvrA and UvrB enhance mutations induced by oxidized deoxyribonucleotides

et al. 2007

View full text Add to dashboard Cite

Oxidatively damaged DNA precursors (deoxyribonucleotides) are formed by reactive oxygen species. After the damaged DNA precursors are incorporated into DNA, they might be removed by DNA repair enzymes. In this study, to examine whether a nucleotide excision repair enzyme, Escherichia coli UvrABC, could suppress the mutations induced by oxidized deoxyribonucleotides in vivo, oxidized DNA precursors, 8-hydroxy-2´-deoxyguanosine 5´-triphosphate and 2-hydroxy-2´-deoxyadenosine 5´-triphosphate, were introduced into uvrA, uvrB, and uvrC E. coli strains, and mutations in the chromosomal rpoB gene were analyzed. Unexpectedly, these oxidized DNA precursors induced mutations only slightly in the uvrA and uvrB strains. In contrast, effect of the uvrC-deficiency was not observed. Next, mutT, mutT/uvrA, and mutT/uvrB E. coli strains were treated with H 2 O 2 , and the rpoB mutant frequencies were calculated. The frequency of the H 2 O 2 -induced mutations was increased in all of the strains tested; however, the increase was threeto four-fold lower in the mutT/uvrA and mutT/uvrB strains than in the mutT strain. Thus, UvrA and UvrB are involved in the enhancement, but not in the suppression, of the mutations induced by these oxidized deoxyribonucleotides. These results suggest a novel role for UvrA and UvrB in the processing of oxidative damage.

show abstract

“…(i) The modified pyrimidines repaired by mNth1 may be repaired by previously undescribed back-up activities. (ii) Nucleotide excision repair activity, which is known to remove Tg residues (17,18,21), may be sufficient to prevent manifestation of a phenotype. (iii) mNth1 may act to prevent pathological consequences resulting from oxidative stresses that were not modeled in our experiments.…”

Section: Discussionmentioning

confidence: 99%

Targeted Deletion of mNth1 Reveals a Novel DNA Repair Enzyme Activity

Ocampo

Chaung

Marenstein

et al. 2002

Molecular and Cellular Biology

View full text Add to dashboard Cite

DNA N-glycosylase/AP (apurinic/apyrimidinic) lyase enzymes of the endonuclease III family (nth in Escherichia coli and Nth1 in mammalian organisms) initiate DNA base excision repair of oxidized ring saturated pyrimidine residues. We generated a null mouse (mNth1 ؊/؊ ) by gene targeting. After almost 2 years, such mice exhibited no overt abnormalities. Tissues of mNth1 ؊/؊ mice contained an enzymatic activity which cleaved DNA at sites of oxidized thymine residues (thymine glycol [Tg]). The activity was greater when Tg was paired with G than with A. This is in contrast to Nth1, which is more active against Tg:A pairs than Tg:G pairs. We suggest that there is a back-up mammalian repair activity which attacks Tg:G pairs with much greater efficiency than Tg:A pairs. The significance of this activity may relate to repair of oxidized 5-methyl cytosine residues (5meCyt). It was shown previously (S. Zuo, R. J. Boorstein, and G. W. Teebor, Nucleic Acids Res. 23:3239-3243, 1995) that both ionizing radiation and chemical oxidation yielded Tg from 5meCyt residues in DNA. Thus, this previously undescribed, and hence novel, back-up enzyme activity may function to repair oxidized 5meCyt residues in DNA while also being sufficient to compensate for the loss of Nth1 in the mutant mice, thereby explaining the noninformative phenotype.Escherichia coli endonuclease III and its eukaryotic homologs initiate the process of DNA base excision repair (BER) of C-5, C-6 ring saturated pyrimidines (31). The endonuclease III-like enzymes are bifunctional enzymes which first effect release of the damaged base from the DNA backbone and then effect strand cleavage at the resulting abasic (apurinic/apyrimidinic [AP]) site via ␤-elimination (19,20,32). Among the modified bases recognized by endonuclease III-like enzymes are 5,6-dihydroxy-5,6-dihydrothymine (thymine glycol [Tg]), cytosine glycol, and cytosine hydrate. Tg is an oxidative product formed in DNA in vitro by reaction with chemical oxidizing agents such as KMnO 4 and OsO 4 as well as via the indirect action of ionizing radiation under aerobic conditions. In cellular DNA, Tg is formed as a product of exposure to aerobic ionizing radiation and other oxidative stresses such as H 2 O 2 in the presence of added Fe 2ϩ . Ionizing irradiation under anaerobic conditions yields the reduced derivative 5,6-dihydrothymine (4, 9, 28). Exposure of cytosine to oxidative stress yields cytosine glycol, which is in equilibrium with its dehydrated form, 5-hydroxycytosine (5ohCyt). 5ohCyt is prone to deamination yielding 5ohUra. In addition to inducing formation of dimeric photoproducts in DNA, UV irradiation also induces hydration of the 5,6 double bond of pyrimidines, primarily forming 5,6 dihydro-6-hydroxy cytosine (cytosine hydrate) (2, 3). Like 5ohCyt, cytosine hydrate is prone to deamination, which yields uracil hydrate (26).Our laboratory first documented the existence of a family of endonuclease III homologs in several species (11) and isolated the cDNA of the human homolog of endonuclease III (hNth...

show abstract

The role of nucleotide excision repair of Escherichia coli in repair of spontaneous and gamma-radiation-induced DNA damage in the lacZα gene

Cited by 9 publications

References 31 publications

An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis

An underlying mechanism for the increased mutagenesis of lagging-strand genes in Bacillus subtilis

UvrA and UvrB enhance mutations induced by oxidized deoxyribonucleotides

Targeted Deletion of mNth1 Reveals a Novel DNA Repair Enzyme Activity

Contact Info

Product

Resources

About