Repair of DNA in Haemophilus Influenzae. II. Excision, Repair of Single-Strand Breaks, Defects in Transformation, and Host Cell Modification in UV-Sensitive Mutants

1968 ◽  
Vol 33 (0) ◽  
pp. 209-218 ◽  
Author(s):  
J. K. Setlow ◽  
M. L. Randolph ◽  
M. E. Boling ◽  
A. Mattingly ◽  
G. Price ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Host Cell ◽  
Excision Repair ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks

scholarly journals DNA DAMAGE AND REPAIR IN EUKARYOTIC CELLS

Genetics ◽  
1974 ◽  
Vol 78 (1) ◽  
pp. 139-148
Author(s):  
R B Painter
Keyword(s):  
Ionizing Radiation ◽  
Excision Repair ◽  
Double Strand Breaks ◽  
Single Strand ◽  
Premature Aging ◽  
Cross Linking ◽  
Base Damage ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Post Replication Repair

ABSTRACT Damage in DNA after irradiation can be classified into five kinds: base damage, single-strand breaks, double-strand breaks, DNA-DNA cross-linking, and DNA-protein cross-linking. Of these, repair of base damage is the best understood. In eukaryotes, at least three repair systems are known that can deal with base damage: photoreactivation, excision repair, and post-replication repair. Photoreactivation is specific for UV-induced damage and occurs widely throughout the biosphere, although it seems to be absent from placental mammals. Excision repair is present in prokaryotes and in animals but does not seem to be present in plants. Post-replication repair is poorly understood. Recent reports indicate that growing points in mammalian DNA simply skip past UV-induced lesions, leaving gaps in newly made DNA that are subsequently filled in by de novo synthesis. Evidence that this concept is oversimplified or incorrect is presented.—Single-strand breaks are induced by ionizing radiation but most cells can rapidly repair most or all of them, even after supralethal doses. The chemistry of the fragments formed when breaks are induced by ionizing radiation is complex and poorly understood. Therefore, the intermediate steps in the repair of single-strand breaks are unknown. Double-strand breaks and the two kinds of cross-linking have been studied very little and almost nothing is known about their mechanisms for repair.—The role of mammalian DNA repair in mutations is not known. Although there is evidence that defective repair can lead to cancer and/or premature aging in humans, the relationship between the molecular defects and the diseased state remains obscure.

scholarly journals Sensitive CometChip assay for screening potentially carcinogenic DNA adducts by trapping DNA repair intermediates

2019 ◽  
Vol 48 (3) ◽  
pp. e13-e13 ◽  
Author(s):  
Le P Ngo ◽  
Norah A Owiti ◽  
Carol Swartz ◽  
John Winters ◽  
Yang Su ◽  
...  
Keyword(s):  
Comet Assay ◽  
Dna Adducts ◽  
Excision Repair ◽  
Environmental Chemicals ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Bulky Dna Adducts ◽  
Dna Strand

Abstract Genotoxicity testing is critical for predicting adverse effects of pharmaceutical, industrial, and environmental chemicals. The alkaline comet assay is an established method for detecting DNA strand breaks, however, the assay does not detect potentially carcinogenic bulky adducts that can arise when metabolic enzymes convert pro-carcinogens into a highly DNA reactive products. To overcome this, we use DNA synthesis inhibitors (hydroxyurea and 1-β-d-arabinofuranosyl cytosine) to trap single strand breaks that are formed during nucleotide excision repair, which primarily removes bulky lesions. In this way, comet-undetectable bulky lesions are converted into comet-detectable single strand breaks. Moreover, we use HepaRG™ cells to recapitulate in vivo metabolic capacity, and leverage the CometChip platform (a higher throughput more sensitive comet assay) to create the ‘HepaCometChip’, enabling the detection of bulky genotoxic lesions that are missed by current genotoxicity screens. The HepaCometChip thus provides a broadly effective approach for detection of bulky DNA adducts.

scholarly journals Accumulation of true single strand breaks and AP sites in base excision repair deficient cells

2010 ◽  
Vol 694 (1-2) ◽  
pp. 65-71 ◽  
Author(s):  
April M. Luke ◽  
Paul D. Chastain ◽  
Brian F. Pachkowski ◽  
Valeriy Afonin ◽  
Shunichi Takeda ◽  
...  
Keyword(s):  
Base Excision Repair ◽  
Excision Repair ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Ap Sites ◽  
Base Excision

A DNA Repair Pathway Polymorphism (rs25487) and Angiographically Proven Coronary Artery Patients in a Population of Southern Iran

2020 ◽  
Vol 18 ◽  
Author(s):  
Seyed Mohammad Hoseini ◽  
Mahdi Bijanzadeh ◽  
Seyed Masoud Seyedian
Keyword(s):  
Dna Repair ◽  
Coronary Artery ◽  
Excision Repair ◽  
Dominant Mode ◽  
Single Strand ◽  
Repair System ◽  
Xrcc1 Gene ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Increased Risk

Background: Coronary artery disease (CAD), which is a multifactorial genetic disease, is known as one of the most common causes of death worldwide. In this regard, X-ray repair cross-complementing group 1 (XRCC1), a DNA repair protein involved in single-strand breaks (SSBs), and base excision repair (BER) pathways have been reported to be responsible for the efficient repair of single strand breaks and damaged bases in DNA. Objective: In the current study, we analyzed Arg399Gln (rs25487), which is one of the most common polymorphism of XRCC1 gene that might be associated with the increased risk for CAD. Method: This case-control study was performed to investigate the relationship between this polymorphism and the CAD development. In this study, 290 patients and 216 controls were diagnosed by cardiac angiography and then screened for the above-mentioned polymorphism using Restriction Fragment Length Polymorphisms (RFLP) method. Results: The frequency of the GA genotype of XRCC1 Arg399Gln (rs25487) was significantly higher in CAD patients compared to the controls (p=0.002, OR: 1.21, 95% CI: 1.06-1.37). Moreover, its dominant mode (AA + GA) genotype had a 1.851-fold increase in the risk of CAD (p = 0.005). Conclusion: Our findings demonstrated that Arg399Gln polymorphism of XRCC1 (rs25487) has a significant relationship with CAD and also plays a probable predisposing role in that. Our results support the role of DNA damages and the malfunctions of DNA repair system in the patients with CAD.

Intermediates in excision repair by human cells: use of S1nuclease and benzoylated naphthoylated cellulose to reveal single-strand breaks

Biochemistry ◽  
1977 ◽  
Vol 16 (20) ◽  
pp. 4483-4490 ◽  
Author(s):  
Peter Karran ◽  
N. Patrick Higgins ◽  
Bernard Strauss
Keyword(s):  
Excision Repair ◽  
Human Cells ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks

scholarly journals Repair of adjacent single-strand breaks is often accompanied by the formation of tandem sequence duplications in plant genomes

2016 ◽  
Vol 113 (26) ◽  
pp. 7266-7271 ◽  
Author(s):  
Simon Schiml ◽  
Friedrich Fauser ◽  
Holger Puchta
Keyword(s):  
Excision Repair ◽  
Strand Break ◽  
Single Strand ◽  
Direct Repeats ◽  
Genomic Context ◽  
Replication Slippage ◽  
Strand Breaks ◽  
Plant Genomes ◽  
Major Mechanism ◽  
Single Strand Breaks

Duplication of existing sequences is a major mechanism of genome evolution. It has been previously shown that duplications can occur by replication slippage, unequal sister chromatid exchange, homologous recombination, and aberrant double-strand break-induced synthesis-dependent strand annealing reactions. In a recent study, the abundant presence of short direct repeats was documented by comparative bioinformatics analysis of different rice genomes, and the hypothesis was put forward that such duplications might arise due to the concerted repair of adjacent single-strand breaks (SSBs). Applying the CRISPR/Cas9 technology, we were able to test this hypothesis experimentally in the model plant Arabidopsis thaliana. Using a Cas9 nickase to induce adjacent genomic SSBs in different regions of the genome (genic, intergenic, and heterochromatic) and at different distances (∼20, 50, and 100 bps), we analyzed the repair outcomes by deep sequencing. In addition to deletions, we regularly detected the formation of direct repeats close to the break sites, independent of the genomic context. The formation of these duplications as well as deletions may be associated with the presence of microhomologies. Most interestingly, we found that even the induction of two SSBs on the same DNA strand can cause genome alterations, albeit at a much lower level. Because such a scenario reflects a natural step during nucleotide excision repair, and given that the germline is set aside only late during development in plants, the repair of adjacent SSBs indeed seems to have an important influence on the shaping of plant genomes during evolution.

scholarly journals XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in Igh genes

2011 ◽  
Vol 208 (11) ◽  
pp. 2209-2216 ◽  
Author(s):  
Huseyin Saribasak ◽  
Robert W. Maul ◽  
Zheng Cao ◽  
Rhonda L. McClure ◽  
William Yang ◽  
...  
Keyword(s):  
B Cells ◽  
Somatic Hypermutation ◽  
Excision Repair ◽  
Single Strand ◽  
Nonhomologous End Joining ◽  
End Joining ◽  
Variable Regions ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Switch Regions

Activation-induced deaminase (AID) deaminates cytosine to uracil in immunoglobulin genes. Uracils in DNA can be recognized by uracil DNA glycosylase and abasic endonuclease to produce single-strand breaks. The breaks are repaired either faithfully by DNA base excision repair (BER) or mutagenically to produce somatic hypermutation (SHM) and class switch recombination (CSR). To unravel the interplay between repair and mutagenesis, we decreased the level of x-ray cross-complementing 1 (XRCC1), a scaffold protein involved in BER. Mice heterozygous for XRCC1 showed a significant increase in the frequencies of SHM in Igh variable regions in Peyer’s patch cells, and of double-strand breaks in the switch regions during CSR. Although the frequency of CSR was normal in Xrcc1+/− splenic B cells, the length of microhomology at the switch junctions decreased, suggesting that XRCC1 also participates in alternative nonhomologous end joining. Furthermore, Xrcc1+/− B cells had reduced Igh/c-myc translocations during CSR, supporting a role for XRCC1 in microhomology-mediated joining. Our results imply that AID-induced single-strand breaks in Igh variable and switch regions become substrates simultaneously for BER and mutagenesis pathways.

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