AID and Reactive Oxygen Species Can Induce DNA Breaks within Human Chromosomal Translocation Fragile Zones

Pannunzio, Nicholas R.; Lieber, Michael R.

doi:10.1016/j.molcel.2017.11.011

Cited by 18 publications

(24 citation statements)

References 71 publications

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“…The stabilization of one strand in an RNA:DNA hybrid can promote secondary structure formation on the exposed non‐template DNA strand . Exposure of single‐stranded DNA (ssDNA) by formation of R‐loops or DNA structures can lead to breaks induced by cytosine deamination and reactive oxygen species …”

Section: Formation Of Secondary Structures In Dnamentioning

confidence: 99%

The role of fork stalling and DNA structures in causing chromosome fragility

Kaushal

Freudenreich

2019

Genes Chromosomes & Cancer

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Alternative non‐B form DNA structures, also called secondary structures, can form in certain DNA sequences under conditions that produce single‐stranded DNA, such as during replication, transcription, and repair. Direct links between secondary structure formation, replication fork stalling, and genomic instability have been found for many repeated DNA sequences that cause disease when they expand. Common fragile sites (CFSs) are known to be AT‐rich and break under replication stress, yet the molecular basis for their fragility is still being investigated. Over the past several years, new evidence has linked both the formation of secondary structures and transcription to fork stalling and fragility of CFSs. How these two events may synergize to cause fragility and the role of nuclease cleavage at secondary structures in rare and CFSs are discussed here. We also highlight evidence for a new hypothesis that secondary structures at CFSs not only initiate fragility but also inhibit healing, resulting in their characteristic appearance.

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Section: Formation Of Secondary Structures In Dnamentioning

confidence: 99%

The role of fork stalling and DNA structures in causing chromosome fragility

Kaushal

Freudenreich

2019

Genes Chromosomes & Cancer

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“…Alternatively, ectopic expression of AID, a cytidine deaminase that targets cytosine residues in ssDNA, was shown previously to enhance R-loop dependent recombination and mutagenesis in yeast [ 13 , 60 ], and could be used to probe R-loop functions at the genome-wide level. Note however that AID could also target ssDNA present in other forms of non-B DNA [ 61 ], which could complicate the interpretation of such experiments.…”

Section: Rnase H Over-expression As a Tool To Probe R-loop Functiomentioning

confidence: 99%

Strengths and Weaknesses of the Current Strategies to Map and Characterize R-Loops

Vanoosthuyse

2018

ncRNA

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R-loops are evolutionarily conserved three-stranded structures that result from the formation of stable DNA:RNA hybrids in the genome. R-loops have attracted increasing interest in recent years as potent regulators of gene expression and genome stability. In particular, their strong association with severe replication stress makes them potential oncogenic structures. Despite their importance, the rules that govern their formation and their dynamics are still controversial and an in-depth description of their direct impact on chromatin organization and DNA transactions is still lacking. To better understand the diversity of R-loop functions, reliable, accurate, and quantitative mapping techniques, as well as functional assays are required. Here, I review the different approaches that are currently used to do so and to highlight their individual strengths and weaknesses. In particular, I review the advantages and disadvantages of using the S9.6 antibody to map R-loops in vivo in an attempt to propose guidelines for best practices.

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“…Thus we subsequently investigated the generation of specific reactive oxygen species with Lyse-It as these species, in particular singlet oxygen ( 1 O 2 ), hydroxyl radicals (•OH), and superoxide anion radicals (O 2 •- ) are known to be associated with intracellular component damage. [27–30] Commercially available off/on fluorescent-based probes were used to detect these radical species during microwave irradiation both with and without Lyse-It. In more oxygenated environments, more ROS were detected as shown by an increase in fluorescence for all of the ROS specific probes.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Elucidation of a non-thermal mechanism for DNA/RNA fragmentation and protein degradation when using Lyse-It

et al. 2019

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Rapid sample preparation is one of the leading bottlenecks to low-cost and efficient sample component detection. To overcome this setback, a technology known as Lyse-It has been developed to rapidly (less than 60 seconds) lyse Gram-positive and–negative bacteria alike, while simultaneously fragmenting DNA/RNA and proteins into tunable sizes. This technology has been used with a variety of organisms, but the underlying mechanism behind how the technology actually works to fragment DNA/RNA and proteins has hitherto been studied. It is generally understood how temperature affects cellular lysing, but for DNA/RNA and protein degradation, the temperature and amount of energy introduced by microwave irradiation of the sample, cannot explain the degradation of the biomolecules to the extent that was being observed. Thus, an investigation into the microwave generation of reactive oxygen species, in particular singlet oxygen, hydroxyl radicals, and superoxide anion radicals, was undertaken. Herein, we probe one aspect, the generation of reactive oxygen species (ROS), which is thought to contribute to a non-thermal mechanism behind biomolecule fragmentation with the Lyse-It technology. By utilizing off/on (Photoinduced electron transfer) PET fluorescent-based probes highly specific for reactive oxygen species, it was found that as oxygen concentration in the sample and/or microwave irradiation power increases, more reactive oxygen species are generated and ultimately, more oxidation and biomolecule fragmentation occurs within the microwave cavity.

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AID and Reactive Oxygen Species Can Induce DNA Breaks within Human Chromosomal Translocation Fragile Zones

Cited by 18 publications

References 71 publications

The role of fork stalling and DNA structures in causing chromosome fragility

The role of fork stalling and DNA structures in causing chromosome fragility

Strengths and Weaknesses of the Current Strategies to Map and Characterize R-Loops

Elucidation of a non-thermal mechanism for DNA/RNA fragmentation and protein degradation when using Lyse-It

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