Consequences and Repair of Oxidative DNA Damage

Duclos, Stéphanie; Doublié, Sylvie; Wallace, Susan S.

doi:10.1039/9781849732925-00115

Cited by 18 publications

(29 citation statements)

References 215 publications

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“…Endogenously produced DNA damages, including oxidative damages, are repaired by the base excision repair (BER) pathway (for reviews see [1–6]). Base excision repair is comprised of five enzymatic steps and is initiated by DNA glycosylases, enzymes which locate and excise a single damaged base leaving an abasic (AP) site in the DNA backbone.…”

Section: Introductionmentioning

confidence: 99%

Insights into the glycosylase search for damage from single-molecule fluorescence microscopy

2014

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The first step of base excision repair utilizes glycosylase enzymes to find damage within a genome. A persistent question in the field of DNA repair is how glycosylases interact with DNA to specifically find and excise target damaged bases with high efficiency and specificity. Ensemble studies have indicated that glycosylase enzymes rely upon both sliding and distributive modes of search, but ensemble methods are limited in their ability to directly observe these modes. Here we review insights into glycosylase scanning behavior gathered through single-molecule fluorescence studies of enzyme interactions with DNA and provide a context for these results in relation to ensemble experiments.

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Section: Introductionmentioning

confidence: 99%

Insights into the glycosylase search for damage from single-molecule fluorescence microscopy

2014

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“…Base excision repair (BER) is a highly conserved pathway from bacteria to humans and is responsible for repairing the vast majority of endogenous DNA damage including alkylations, oxidations, deaminations and depurinations, as well as single-strand breaks (SSBs) (for reviews see [1,2]. Thus, the primary function of BER is to remove these frequently produced lesions and maintain genomic integrity.…”

Section: Base Excision Repair Overviewmentioning

confidence: 99%

“…Organisms from bacteria to humans have evolved multiple mechanisms to deal with this problem (for reviews see [1,3]). Both 8-oxoG and FapyG opposite C are the preferred substrates for OGG.…”

Section: Base Excision Repair and Cancermentioning

confidence: 99%

Base excision repair: A critical player in many games

2014

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This perspective reviews the many dimensions of base excision repair from a 10,000 foot vantage point and provides one person’s view on where the field is headed. Enzyme function is considered under the lens of X-ray diffraction and single molecule studies. Base excision repair in chromatin and telomeres, regulation of expression and the role of posttranslational modifications are also discussed in the context of enzyme activities, cellular localization and interacting partners. The specialized roles that base excision repair play in transcriptional activation by active demethylation and targeted oxidation as well as how base excision repair functions in the immune processes of somatic hypermutation and class switch recombination and its possible involvement in retroviral infection are also discussed. Finally the complexities of oxidative damage and its repair and its link to neurodegenerative disorders, as well as the role of base excision repair as a tumor suppressor are examined in the context of damage, repair and aging. By outlining the many base excision repair-related mysteries that have yet to be unraveled, hopefully this perspective will stimulate further interest in the field.

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“…BER evolved to protect cellular DNA against the deleterious effects of endogenous metabolic processes, as well as damage produced by exogenous agents such as ionizing radiation (David et al, 2007; Duclos et al, 2012; Kim and Wilson, 2012; Prakash et al, 2012; Wallace, 2013; Wilson et al, 2003). In fact, the great majority of damages produced by ionizing radiation are repaired by BER (Wallace, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…The lyase products, an α,β-unsaturated aldehyde (Nth) or a phosphate (Fpg and Nei), are removed by an apurinic (AP) endonuclease. The gap is filled in by a DNA polymerase and sealed by DNA ligase (Duclos et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

Visualizing the search for radiation-damaged DNA bases in real time

Lee

Wallace

2016

Radiation Physics and Chemistry

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The Base Excision Repair (BER) pathway removes the vast majority of damages produced by ionizing radiation, including the plethora of radiation-damaged purines and pyrimidines. The first enzymes in the BER pathway are DNA glycosylases, which are responsible for finding and removing the damaged base. Although much is known about the biochemistry of DNA glycosylases, how these enzymes locate their specific damage substrates among an excess of undamaged bases has long remained a mystery. Here we describe the use of single molecule fluorescence to observe the bacterial DNA glycosylases, Nth, Fpg and Nei, scanning along undamaged and damaged DNA. We show that all three enzymes randomly diffuse on the DNA molecule and employ a wedge residue to search for and locate damage. The search behavior of the Escherichia coli DNA glycosylases likely provides a paradigm for their homologous mammalian counterparts.

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Consequences and Repair of Oxidative DNA Damage

Cited by 18 publications

References 215 publications

Insights into the glycosylase search for damage from single-molecule fluorescence microscopy

Insights into the glycosylase search for damage from single-molecule fluorescence microscopy

Base excision repair: A critical player in many games

Visualizing the search for radiation-damaged DNA bases in real time

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