Base-excision repair of oxidative DNA damage

David, Sheila S.; O’Shea, Valerie L.; Kundu, Sucharita

doi:10.1038/nature05978

Cited by 1,055 publications

(1,169 citation statements)

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“…One of the most common reactive oxygen speciesmediated DNA modification is the conversion of guanine to 7, 8-dihydro-8-oxoguanine (also known as 8-oxoguanine; 8-oxoG) (David et al, 2007). This damage can lead to mutations in nuclear and/or mitochondrial DNA, but can also cause epigenetic alterations, leading to cellular dysregulation and malignant transformation.…”

Section: Starvation and Stress Resistancementioning

confidence: 99%

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

2011

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Section: Starvation and Stress Resistancementioning

confidence: 99%

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

2011

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“…The small 8-oxoG lesion is highly prevalent (Box 2); hence, it is inevitable that high-fidelity processive DNA polymerases will encounter this lesion, despite the activity of specific repair enzymes, which scan DNA to locate and repair it [35]. Biochemical processing and X-ray crystal-lographic studies of DNA containing 8-oxoG in complexes with BF [25] and Dpo4 [14,26] have highlighted striking differences in how these polymerases cope with this oxidative guanine lesion.…”

Section: Small Lesion Processing: 8-oxog Bf Favors 8-oxog-a Mispairingmentioning

confidence: 99%

Lesion processing: high-fidelity versus lesion-bypass DNA polymerases

Broyde¹,

Wang²,

Rechkoblit³

et al. 2008

Trends in Biochemical Sciences

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When a high-fidelity DNA polymerase encounters certain DNA-damage sites, its progress can be stalled and one or more lesion-bypass polymerases are recruited to transit the lesion. Here, we consider two representative types of lesions: (i) 7,8-dihydro-8-oxogua-nine (8-oxoG), a small, highly prevalent lesion caused by oxidative damage; and (ii) bulky lesions derived from the environmental pre-carcinogen benzo [a]pyrene, in the high-fidelity DNA polymerase Bacillus fragment (BF) from Bacillus stearothermophilus and in the lesion-bypass DNA polymerase IV (Dpo4) from Sulfolobus solfataricus. The tight fit of the BF polymerase around the nascent base pair contrasts with the more spacious, solvent-exposed active site of Dpo4, and these differences in architecture result in distinctions in their respective functions: one-step versus stepwise polymerase translocation, mutagenic versus accurate bypass of 8-oxoG, and polymerase stalling versus mutagenic bypass at bulky benzo[a]pyrene-derived lesions. Lesions and DNA polymerasesUntil 1999, it was widely understood that bacteria have three DNA polymerases and mammals have five [1]. In 1999, however, an entirely new category of polymerases was discovered in prokaryotes and eukaryotes [2-4] -the lesion-bypass DNA polymerases. The function of lesion-bypass polymerases is to replicate past lesion-containing DNA templates in a process called translesion synthesis [5][6][7]. Now at least 16 DNA polymerases are known in eukaryotes [8] and five in bacteria [9]. Furthermore, since 1999, crystal structures of DNA polymerases, including those containing lesions, have provided new structural insights into the mechanistic aspects of translesion synthesis and polymerase stalling associated with DNA lesions. For a review of the structures and mechanisms of DNA polymerases up to the year 2005, see Ref.[10].Here, we discuss the structural and functional features of representative high-fidelity and lesion-bypass DNA polymerases (Box 1) and how these features affect the processing of certain forms of DNA damage. The lesions considered are derived from reactions of intermediates produced by endogenous sources or from the metabolic activation of environmental genotoxic

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“…OGG1 participates in the recognition and elimination of the genome of 8-oxoguanine, a potentially mutagenic product resulting from oxidative damage [53,54]. The deletion of OGG1 in mice exacerbates lung injury following P. aeruginosa infection compared with control mice, highlighting the important role of OGG1 in protection and DNA repair [53].…”

Section: Pseudomonas and Dna Damagementioning

confidence: 99%

When our genome is targeted by pathogenic bacteria

Lemercier

2015

Cell. Mol. Life Sci.

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Eukaryotic cells repair thousands of lesions arising in the genome at each cell cycle. The most hazardous damage is likely DNA doublestrand breaks (DSB) that cleave the double helix backbone. DSBs occur naturally during T-cell receptor and immunoglobulin gene recombination in lymphocytes. DSBs can also arise as a consequence of exogenous stresses (e.g. ionizing irradiation, chemotherapeutic drugs, viruses) or oxidative processes. An increasing number of studies have reported that infection with pathogenic bacteria also alters the host genome, producing DSB and other modifications on DNA. This review focuses on recent data on bacteria-induced DNA damage and the known strategies used by these pathogens to maintain a physiological niche in the host. Even after DNA repair in infected cells, "scars" often remain on chromosomes and might generate genomic instability at the next cell division. Chronic inflammation in tissue, combined with infection and DNA damage, can give rise to genomic instability and eventually cancer. A functional link between the DNA damage response and the innate immune response has been recently established. Pathogenic bacteria also highjack the host cell cycle, often acting on the stability of the master regulator p53, or dampen the DNA damage response to support bacterial replication in an appropriate reservoir. Except in a few cases, the molecular mechanisms responsible for DNA lesions are poorly understood, although ROS release during infection is a serious candidate for generating DNA breaks. Thus, chronic or repetitive infections with genotoxic bacteria represent a common source of DNA lesions that compromise host genome integrity.

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Base-excision repair of oxidative DNA damage

Cited by 1,055 publications

References 109 publications

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

Lesion processing: high-fidelity versus lesion-bypass DNA polymerases

When our genome is targeted by pathogenic bacteria

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