Mechanism of DNA strand nicking at apurinic/apyrimidinic sites by <i>Escherichia coli</i> [formamidopyrimidine]DNA glycosylase

Bailly, Véronique; Verly, Walter G.; O’Connor, Tim; Laval, Jacques

doi:10.1042/bj2620581

Cited by 155 publications

(97 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high G+C content (~65 mol%) of the genomes of mycobacteria puts them at a greater risk of cytosine deamination (to uracil), and oxidative damage of guanosine (to 8-oxoG). The pathways that repair uracil and 8-oxoG are initiated by uracil DNA glycosylase (Ung or UDG; Lindahl, 1979;Duncan, 1981;Krokan et al, 1997) and formamidopyrimidine DNA glycosylase (Fpg or MutM, Bailly et al, 1989;Tchou et al, 1991;Graves et al, 1992), respectively, which are also two important BER enzymes in mycobacteria (Venkatesh et al, 2003;Jain et al, 2007). On the other hand, UvrB is a central player in NER (Skorvaga et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

et al. 2008

View full text Add to dashboard Cite

Mycobacteria are an important group of human pathogens. Although the DNA repair mechanisms in mycobacteria are not well understood, these are vital for the pathogen's persistence in the host macrophages. In this study, we generated a null mutation in the uvrB gene of Mycobacterium smegmatis to allow us to compare the significance of the nucleotide excision repair (NER) pathway with two important base excision repair pathways, initiated by uracil DNA glycosylase (Ung) and formamidopyrimidine DNA glycosylase (Fpg or MutM), in an isogenic strain background. The strain deficient in NER was the most sensitive to commonly encountered DNAdamaging agents such as UV, low pH, reactive oxygen species, hypoxia, and was also sensitive to acidified nitrite. Taken together with previous observations on NER-deficient M. tuberculosis, these results suggest that NER is an important DNA repair pathway in mycobacteria.

show abstract

Section: Introductionmentioning

confidence: 99%

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The 5Ј-end group generated by endonucleases III and VIII was a terminal phosphate, whereas the 5Ј-end group generated by endonuclease IV was a deoxyribose. The single nucleotide gap with a 3Ј-hydroxyl and a 5Ј-phosphate was made by incubating the AP site-containing transcription template with endonuclease IV followed by formamidopyrimidine DNA glycosylase (Fpg) (laboratory stock) (43).…”

Section: Introduction Of Unique Damages To Transcriptionmentioning

confidence: 99%

Single-Stranded Breaks in DNA but Not Oxidative DNA Base Damages Block Transcriptional Elongation by RNA Polymerase II in HeLa Cell Nuclear Extracts

Kathe¹,

Shen

Wallace

2004

Journal of Biological Chemistry

135

105

View full text Add to dashboard Cite

Transcription and repair of many DNA helix-distorting lesions such as cyclobutane pyrimidine dimers have been shown to be coupled in cells across phyla from bacteria to humans. The signal for transcription-coupled repair appears to be a stalled transcription complex at the lesion site. To determine whether oxidative DNA lesions can block correctly initiated human RNA polymerase II, we examined the effect of site-specifically introduced oxidative damages on transcription in HeLa cell nuclear extracts. We found that transcription was blocked by single-stranded breaks, common oxidative DNA lesions, when present in the transcribed strand of the transcription template. Cyclobutane pyrimidine dimers, which have been previously shown to block transcription both in vitro and in vivo, also blocked transcription in the HeLa cell nuclear transcription assay. In contrast, the oxidative DNA base lesions, 8-oxoguanine, 5-hydroxycytosine, and thymine glycol did not inhibit transcription, although pausing was observed with the thymine glycol lesion. Thus, DNA strand breaks but not oxidative DNA base damages blocked transcription by RNA polymerase II.Transcription-coupled repair (TCR) 1 is a specialized form of DNA repair where damages are repaired preferentially in the transcribed strand of actively transcribed genes (for reviews, see Refs. 1 and 2). TCR was originally believed to be a subpathway of nucleotide excision repair; however, ionizing radiation damage (3), 5,6-dihydroxy-5,6-dihydrothymine (thymine glycol; Tg) (4, 5), and 7,8-dihydro-8-oxoguanine (8-oxoG) (5) are removed in a TCR-dependent manner from human cells that lack nucleotide excision repair. Since Tg and 8-oxoG are small nonbulky lesions that are repaired primarily by the base excision repair (BER) pathway (for reviews, see Refs. 6 -8), TCR of Tg and 8-oxoG in cells that lack nucleotide excision repair (5) links TCR to BER. TCR of 8-oxoG has also been shown to occur in nonreplicating Escherichia coli cells (9). TCR of oxidative damage does not appear to be universal, since in Chinese hamster ovary cells, TCR of oxidative damage produced by photosensitization and oxidizing agents is not observed in the Dhfr and cFos genes (10 -12). Furthermore, DNA strand breaks, oxidative lesions also repaired by BER, do not appear to be repaired by TCR in the Dhfr gene from Chinese hamster ovary cells (13) or human colon cancer cells (14). Interestingly, recent measurements of TCR of cyclobutane pyrimidine dimers in the Hprt gene, integrated at different sites in Chinese hamster ovary cell chromosomes, have suggested that preferential repair of actively transcribed genes, as well as preferential repair of damages in the transcribed strand, is significantly affected by genomic context (15).The proposed signal for TCR is an RNA polymerase transcription complex stalled at a lesion, which recruits the repair proteins to the damage site (16 -18); the ability of a lesion on the transcribed strand to block the RNA polymerase transcription complex has been assumed to be crucial for T...

show abstract

“…Catalysis by both E. coli Nei (EcoNei) and Fpg (EcoFpg) is by means of the N-terminal proline, which forms a Schiff base with the oxidized lesion (13)(14)(15). Both EcoNei and EcoFpg are trifunctional enzymes containing glycosylase, ␤,␦ lyase, and 5Ј phosphodiesterase activities (16)(17)(18)(19). Fpg and Nei also share common structural motifs, including helix-two-turns-helix (H2TH) and antiparallel ␤-hairpin zinc finger motifs (6,12).…”

mentioning

confidence: 99%

The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity

Doublié

Bandaru

Bond

et al. 2004

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

137

194

View full text Add to dashboard Cite

In prokaryotes, two DNA glycosylases recognize and excise oxidized pyrimidines: endonuclease III (Nth) and endonuclease VIII (Nei). The oxidized purine 8-oxoguanine, on the other hand, is recognized by Fpg (also known as MutM), a glycosylase that belongs to the same family as Nei. The recent availability of the human genome sequence allowed the identification of three human homologs of Escherichia coli Nei. We report here the crystal structure of a human Nei-like (NEIL) enzyme, NEIL1. The structure of NEIL1 exhibits the same overall fold as E. coli Nei, albeit with an unexpected twist. Sequence alignments had predicted that NEIL1 would lack a zinc finger, and it was therefore expected to use a different DNA-binding motif instead. Our structure revealed that, to the contrary, NEIL1 contains a structural motif composed of two antiparallel ␤-strands that mimics the antiparallel ␤-hairpin zinc finger found in other Fpg͞Nei family members but lacks the loops that harbor the zinc-binding residues and, therefore, does not coordinate zinc. This ''zincless finger'' appears to be required for NEIL1 activity, because mutating a very highly conserved arginine within this motif greatly reduces the glycosylase activity of the enzyme.

show abstract

Mechanism of DNA strand nicking at apurinic/apyrimidinic sites by Escherichia coli [formamidopyrimidine]DNA glycosylase

Cited by 155 publications

References 12 publications

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

Important role of the nucleotide excision repair pathway in Mycobacterium smegmatis in conferring protection against commonly encountered DNA-damaging agents

Single-Stranded Breaks in DNA but Not Oxidative DNA Base Damages Block Transcriptional Elongation by RNA Polymerase II in HeLa Cell Nuclear Extracts

The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity

Contact Info

Product

Resources

About