SEARCH · PubMed Health

Results for “Excision Repair”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1979

Enhancement of excision-repair efficiency by conditioned medium from density-inhibited cultures in V79 Chinese hamster cells: evidence for excision repair as an error-free repair process.

Conditioned medium from density-inhibited V79 Chinese hamster cell cultures, given as a post-treatment to UV-irradiated homologous cells, was demonstrated to reduce the lethal action of ultraviolet light by temporarily blocking DNA replication. Since the increased survival was not affected by various non-toxic concentrations of caffeine, such protective effect would be attributable to the prolonged intervention of excision repair before DNA replication during the post-treatment period. The influence of conditioned medium on the UV-induced mutation at the ouabain-resistance locus was also examined and a significant decrease in mutation frequency was noted. The observed reduction in killing and mutation as a result of post-incubation in conditioned medium, which delays DNA replication, would be interpreted as evidence that conditioned medium provides a longer period of time for an error-free excision-repair process, leaving lesion in DNA available for error-prone post-replication repair.

Animals↗

PubMed1979

DNA repair in Bacillus subtilis: excision repair capacity of competent cells.

Competent Bacillus subtilis were investigated for their ability to support the repair of UV-irradiated bacteriophage and bacteriophage DNA. UV-irradiated bacteriophage DNA cannot be repaired to the same level as UV-irradiated bacteriophage, suggesting a deficiency in the ability of competent cells to repair UV damage. However, competent cells were as repair proficient as noncompetent cells in their ability to repair irradiated bacteriophage in marker rescue experiments. The increased sensitivity of irradiated DNA is shown to be due to the inability of excision repair to function on transfecting DNA in competent bacteria. Furthermore, competent cells show no evidence of possessing an inducible BsuR restriction system to complement their inducible BsuR modification enzyme.

Bacillus subtilis↗

PubMed2026

Navigating the base excision repair pathway in chromatin-focus on oxidative DNA damage.

Chromatin environment influences all nuclear processes, including DNA repair. Conversely, DNA damage itself triggers chromatin modifications and remodeling, which are essential for efficient DNA repair and its coordination with transcription, replication, and epigenetic regulation to preserve genome function. While chromatin dynamics associated with double-strand break repair and nucleotide excision repair are well understood, those accompanying base excision repair (BER) remain comparatively poorly characterized. Yet, BER is responsible for eliminating a wide spectrum of chemically diverse and non-helix-distorting base modifications, arising from both endogenous and exogenous sources, and is implicated in numerous pathologies. This review examines how BER operates in the context of chromatin, with a focus on its interplay with other repair factors, chromatin modifications, and remodeling. It also explores the diversity of BER substrates, the blurred distinction between base lesions and programmed modifications, and the intricate link between BER, transcriptional regulation, and epigenetic reprogramming. Together, these insights highlight BER's pivotal role in maintaining genome stability, shaping transcriptional programs, and preventing disease.

Excision Repair↗

PubMed1976

Excision repair of DNA in some photodermatoses.

Excision repair of DNA was measured in a number of photosensitive subjects by estimating unscheduled DNA synthesis in cultured fibroblasts after ultraviolet radiation. The amount of unscheduled DNA synthesis and the action spectrum for this process were estimated in each subject and compared with seven normal subjects. Two subjects with polymorphic light eruption and three with actinic reticuloid exhibited normal levels of DNA repair and normal action spectra. In one subject with classical xeroderma pigmentosum no excision repair could be demonstrated whilst in another the amount of repair was lower than normal. The finding of normal DNA excision repair in polymorphic light eruption does not support an earlier claim that this repair process is abnormal in this common photodermatosis.

Adult↗

PubMed1975

Enzymic mechanism of excision-repair in T4-infected cells.

Excision of pyrimidine dimers from ultraviolet-irradiated DNA in a cell-free system of Escherichia coli infected with bacteriophage T4 consists of two different steps, one to induce a single-strand break at a point close to a pyrimidine dimer and the other to release dimer-containing nucleotide from the DNA. The enzymes responsible for these steps were isolated and the reactions were characterized; T4 endonuclease V introduces a break at the 5' side of a dimer and 5' in equilibrium 3' exonucleases, which are also induced by T4, act at the break to excise dimer-containing nucleotides. We isolated temperature-dependent v mutants, which exhibit increased sensitivity to UV at 42 degrees C but not at 30 degrees C, and found that the mutants induce temperature-sensitive T4 endonuclease V, indicating that the v gene of T4 is indeed the structural gene for T4 endonuclease V and that the enzyme is responsible for the first step of excision-repair. A possible mechanism of excision-repair in T4-infected cells is discussed.

Coliphages↗

PubMed1975

A mutant of Eshcerchia coli K-12, URT-43, with a temperature-sensitive defect at the incision step of the excision repair mechanism.

URT-43, which has a defect in excision repair, exhibits a temperature-dependent ultraviolet survival. It was shown that URT-43 requires protein synthesis but not DNA synthesis for recovery, by examining recovery in a growth medium containing chloramphenicol or nalidixic acid. The recovery of irradiated bacteriophage lambda in URT-43 took place in a medium containing nalidixic acid at 30 degrees, but not at 41 degrees, and chloramphenicol prevented this recovery. These results seem to imply that the product of the mutated gene in URT-43 is labile. URT-43 was confirmed to have a temperature-sensitive mutation at the incision step of the excision repair mechanism by examining the nick formation of parental DNA in alkaline sucrose gradients. The release of pyrimidine dimers was reinvestigated directly by one- and two-dimensional paper-chromatography and indirectly by examining the distribution of DNA molecules synthesized after irradiation. Dimers were excised into the acid-soluble fraction when growing bacteria were incubated, but were not excised when in amino acid starved bacteria. These results suggest that URT-43 is a mutant slowly excising pyrimidine dimers because the product of a mutated gene concerned with the incision step of the excision repair mechanism is unstable.

Centrifugation, Zonal↗

PubMed1975

Physico-chemical and biological study of excision-repair of UV--irradiated phiX174 RF DNA in vitro.

We have studied excision-repair of UV-irradiated phiX174 RFI DNA in vitro with UV-specific endonuclease from Micrococcus luteus (UV-endo), DNA polymerase I from Escherichia coli and DNA ligase from phage T4 infected E. coli. Excision-repair was measured a) by physico-chemical methods, i.e. by determination of the conversion of RF I DNA into RF II DNA by UV-endo and by the subsequent conversion of RF II DNA ligase, b) by biological methods i. e. by measuring the ability of the reaction product to form phages upon incubation with spheroplasts from the appropriate strains of E. coli. Using the first method, we have shown, that more than 90% of the pyrimidine dimers can be repaired in vitro; with the latter method we have shown, that the molecules which are repaired as defined by method a) have regained full biological activity. Exonuclease III was found to be not essential for excision-repair in vitro and also did not stimulate repair. From this result we conclude that UV-endo generates 3'OH endgroups, in agreement with results obtained by Hamilton et al. (1974). The usefulness of the method presented in this paper with regard to the study of excision-repair is discussed.

Chemical Phenomena↗

PubMed1976

Effect of excision repair on azide-induced mutagenesis.

Azide mutagenesis was investigated in Salmonella typhimurium and Escherichia coli. Azide was highly effective in inducing his+ revertants in excision-repair deficient (uvrB) derivatives of S. typhimurium hisG46 and in inducing high frequencies of 5-fluorouracil resistant mutants in excision-repair deficient (uvrA) derivatives of E. coli B/r WP2. In excision-repair plus strains, azide was only a marginal or ineffective mutagen, demonstrating that the bacterial excision-repair system could repair nearly all azide-induced damage. This observation suggests that the initial azide-induced lesion causes a major DNA helix distortion recognizable by the excision-repair endonucleases. The presence of recombination deficient (recB or recC) genes in combination with uvrA increased E. coli sensitivity to azide killing, but depressed azide mutagenicity. These results are similar to those reported for UV-induced mutagenesis with the E. coli strains and suggest that post-replication repair might be the error-prone step in the repair process. Azide mutagenesis specificity is, however, unique and different from UV, as demonstrated by inability of azide to revert the ochre try locus in E. coli WP2s. These results show that the initial azide-induced DNA damage is highly specific but different from UV-induced DNA damage. Metabolic inhibitors, similar in action to azide, did not induce mutations in S. typhimurium strain TA1530, a strain highly susceptible to azide mutagenesis, thus ruling out the possibility that azide mutagenesis was due to peroxide accumulation. A mechanism based on in vivo activation of azide to the actual mutagen is proposed.

Azides↗

PubMed1975

Dependence upon growth medium and the polA, polC, recA, recB, recC, and exrA genes of separate branches of the uvr Gene-dependent excision-repair process in Escherichia coli K12 cells.

The repair of single-strand breaks which arise in DNA during the uvr gene-dependent excision-repair process was examined in certain radiation-sensitive strains of Escherichia coli K12. The results suggest that the excision-repair process may be divided into two branches, one which is dependent on the presence of growth medium and also the rec+ exr+ genotype, and a second which can occur in buffer (growth medium independent) and is largely dependent on DNA polymerase I. DNA polymerase III appears to be involved in the growth-medium-dependent branch of excision repair, and also in the residual growth-medium-independent repair which occurs in polA1 cells. Chloramphenicol, dinitrophenol, and impurities present in some brands of agar all appear to inhibit the growth-medium-dependent branch of excision-repair. The similarities of the two branches of excision-repair to two known pathways for the repair of X-ray-induced DNA chain breaks are discussed.

Chloramphenicol↗

PubMed1979

Recovery of DNA synthesis after ultraviolet irradiation of xeroderma pigmentosum cells depends on excision repair and is blocked by caffeine.

Normal human and xeroderma pigmentosum (XP, excision-defective group A) cells (both SV40-transformed) pulse-labeled with [(3)H]thymidine at various times after irradiation with ultraviolet light showed a decline and recovery of both the molecular weights of newly synthesized DNA and the rates of synthesis per cell. At the same ultraviolet dose, both molecular weights and rates of synthesis were inhibited more in XP than in normal cells. This indicates that excision repair plays a role in minimizing the inhibition of chain growth, possibly by excision of dimers ahead of the growing point. The ability to synthesize normal-sized DNA recovered more rapidly than rates of synthesis in normal cells, but both parameters recovered in phase in XP cells. During recovery in normal cells there are therefore fewer actively replicating clusters of replicons because the single-strand breaks involved in the excision of dimers inhibit replicon initiation. XP cells have few excision repair events and therefore fewer breaks to interfere with initiation, but chain growth is blocked by unexcised dimers. In both cell types recovery of the ability to synthesize normal-sized DNA was prevented by growing cells in caffeine after irradiation, possibly because of competition between the DNA binding properties of caffeine and replication proteins. Our observations imply that excision repair and semiconservative replication interact strongly in irradiated cells to produce a complex spectrum of changes in DNA replication which may be confused with parts of alternative systems such as post-replication repair.

Caffeine↗

PubMed2026

Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.

PURPOSE: Base excision repair (BER) is the predominant pathway for repairing non‑bulky oxidized and alkylated DNA base lesions, and its fidelity depends on the coordinated action of lesion‑specific DNA glycosylases and downstream repair enzymes. This review aims to summarize recent structural, biochemical, and genomic insights into three base excision repair enzymes, MUTYH DNA glycosylase, NTHL1 DNA glycosylase, and DNA polymerase β. CONCLUSION: This review outlines how MUTYH, NTHL1 and DNA polymerase β protect the genome from mutagenesis, highlights major germline variants associated with disease, and synthesizes the current knowledge on the characteristic single base substitution (SBS) mutational signatures that occur when these repair enzymes are dysfunctional.

Base excision repair↗

PubMed1979

uvrC gene function in excision repair in toluene-treated Escherichia coli.

We have examined the role of the uvrC gene in UV excision repair by studying incision, excision, repair synthesis, and DNA strand reformation in Escherichia coli mutants made permeable to nucleoside triphosphates by toluene treatment. After irradiation, incisions occur normally in uvrC cells in the presence of nicotinamide mononucleotide (NMN), a ligase-blocking agent, but cannot be detected otherwise. We conclude that repair incisions are followed by a ligation event in uvrC mutants, masking incision. However, a uvrC polA12 mutant accumulates incisions only slightly less efficiently than a polA12 strain without NMN. Excision of pyrimidine dimers is defective in uvrC mutants (polA(+) or polA12) irrespective of the presence or absence of NMN. DNA polymerase I-dependent, NMN-stimulated repair synthesis, which is demonstrable in wild-type cells, is absent in uvrC polA(+) cells, but the uvrC polA12 mutant exhibits a UV-specific, ATP-dependent repair synthesis like parental polA12 strains. A DNA polymerase I-mediated reformation of high-molecular-weight DNA takes place efficiently in uvrC polA(+) mutants after incision accumulation, and the uvrC polA12 mutant shows more reformation than the polA12 strain after incision. These results indicate that normal incision occurs in uvrC mutants, but there appears to be a defect in the excision of pyrimidine dimers, allowing resealing via ligation at the site of the incision. The lack of NMN-stimulated repair synthesis in uvrC polA(+) cells indicates that incision is not the only requirement for repair synthesis.

DNA Polymerase I↗

PubMed1979

DNA excision-repair processes in human cells can eliminate the cytotoxic and mutagenic consequences of ultraviolet irradiation.

The ability of DNA excision-repair processes in diploid human fibroblasts to eliminate potentially cytotoxic and mutagenic lesions induced by UV radiation (254 nm) was demonstrated in two ways: (1) Cells with normal rates of excision were compared with cells with an intermediate rate of excision (XP2BE) and cells with an excision rate less than or equal to 1% that of normal (XP12BE) for sensitivity to the killing and mutagenic action of UV radiation. The normal cells proved resistant to doses of UV which reduced the survival of the XP cells to 14% and 0.7%, respectively, and increased the frequency of mutations to 8-azaguanine resistance in the XP cells 5- to 10-fold over background. (2) Cells in confluence were irradiated with cytotoxic and mutagenic doses of UV and allowed to carry out excision repair. After various lengths of time they were replated at lower densities to allow for expression of mutations to 6-thioguanine resistance and/or at cloning densities to assay survival. Normal cells and XP cells with reduced rates of excision repair (from complementation groups C and D) exhibited a gradual increase in survival from an initial level of 15--20% to 100% if held approximately 20 h in confluence. In contrast, XP12BE cells showed no increase from an initial survival of 20% even when held for 7 days. Normal cells irradiated in confluence but prevented from replicating for 7 days exhibited background mutation frequencies, whereas the mutation frequency in XP12BE cells did not change with the time in confluence.

Cell Line↗

PubMed1977

Expression of an excision repair gene in transformation of Bacillus subtilis.

DNA of Bacillus subtilis proficient in excision repair (hcr+) was introduced into Angiografinpurified competent cells of an excision repair-deficient strains UVS-1 (hcr-1). The hcr+ gene was found to affect the UV-survival curve of the cells, giving rise to a UV-resistant component. However, a considerable number of colonies of the UV-resistant component consisted of cells that were not transformed to hcr+ as judged by their sensitivity to mitomycin C (MC), UV, and by their ability to reactivate UV-irradiated M2 phages. This suggests that the hcr gene may be expressed without integration. The recA function of B. subtilis was necessary for expression of UV resistance to occur. When DNA-treated cells were selected for met+ recombinants, the UV-resistant component was again found on the UV-survival curve and about half of the colonies of the UV-resistant component consisted of Hcr- cells. This result was explained by an integration-segregation model for hcr+ and met+ genes. The effect of the hcr+ gene was seen even when DNA was added after cells were irradiated with UV, although this effect was gradually diminished by delaying the time of DNA addition. A complementation effect was found between two excision repair mutations residing in two distant loci, using hcr-114 DNA as a donor and hcr-1 cells as a recipient.

Bacillus subtilis↗

PubMed2026

Vitamin D Supplementation Modulates Base Excision Repair (BER) Machinery in Systemic Sclerosis: A Prospective Longitudinal Study.

Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicated in its pathogenesis, the impact of vitamin D on DNA repair pathways remains unclear. This study aimed to investigate the expression of DNA repair enzymes in SSc, explore their relationship with vitamin D status and assess the effects of vitamin D supplementation on the transcriptional expression of these enzymes. Peripheral blood samples were collected from 52 female patients with SSc and 31 age-matched healthy controls (HCs). Gene expression levels of base excision repair (BER) enzymes (APE1 and OGG1) and nucleotide excision repair (NER) enzymes (XPA and XPC) were analyzed. Serum vitamin D levels were measured and correlated with disease activity scores. In a prospective arm of the study, patients received six months of vitamin D supplementation and their DNA repair capacity was evaluated pre- and post-intervention. Baseline expression of APE1 and OGG1 was significantly lower in SSc patients than in HCs, whereas expression of the NER genes remained unchanged, indicating selective impairment of the BER pathway. Vitamin D deficiency was prevalent in SSc and inversely correlated with disease severity. Supplementation significantly increased serum vitamin D levels and up-regulated APE1 and OGG1 expression; while NER genes remained unaffected. These findings are consistent with evidence of elevated oxidative DNA lesions in SSc and support a mechanistic link between BER activity and the repair of oxidative DNA damage. SSc patients exhibit reduced transcription of BER-specific enzymes associated with vitamin D deficiency andrestoration of vitamin D levels partially rescues BER enzyme expression. These findingshighlight a potentially modifiable axis linking micronutrient status, genomic stability and disease activity and provide a rationale for investigating vitamin D optimization as an adjunctive strategy to enhance DNA repair and potentially attenuate inflammatory and fibrotic processes in SSc.

Humans↗

PubMed1975

Excision-repair of 4-nitroquinolin-1-oxide damage responsible for killing, mutation, and cancer.

Excision-repair of DNA base damage produced by 4-nitroquinoline-1-oxide (4NQO) was compared in Escherichia coli, human cells, and mouse cells. Paper chromotography of acid hydrolysates of DNA extracted from cells treated with 3H-labeled 4NQO revealed four peaks; two kinds of 4NQO-guanine adduct, one kind of 4NQO-adenine adduct, and free 4-aminoquinoline-1-oxide (4AQO). About 80% of the initially formed 4NQO-purine adducts were excised from DNA in E. coli uvrA+ cells during 60 min postincubation, but not at all in uvrA- (excisionless for uv damage) cells. Normal human cells excised about 60% of 4NQO-purine adducts during 24 hr postincubation, but xeroderma pigmentosum (excisionless) cells did not. A mouse cell line susceptible to repair of 4NQO-induced pretransformational damage also showed excision-repair ability for the 4NQO adducts. From these and other results, we conclude that the 4NQO-purine adducts and unstable 4NQO-guanine products (which release 4AQO) are, like pyrimidine dimers, repairable by excision-repair universal among E. coli, mouse, and human being, and that unexcised ones are probably the major cause of killing, mutation, and cancer.

4-Nitroquinoline-1-oxide↗

PubMed1979

Mutagenicity of cross-links and monoadducts of furocoumarins (psoralen and angelicin) induced by 360-nm radiation in excision-repair-defective and radiation-insensitive strains of Saccharomyces cerevisiae.

The furocoumarin psoralen can form both monoadducts and cross-links with DNA when combined with 360-nm radiation, whereas the analog angelicin can form monoadducts only. Psoralen plus 360-nm radiation causes mutation induction with a slope of 2 (log-log plot) for a radiation-insensitive strain, whereas angelicin action with 360-nm radiation displays a slope of unity. For a radiation-sensitive mutant defective in the excision-repair pathway, the actions of both angelicin and psoralen plus 360-nm radiation exhibit one-target kinetics, but at higher exposures psoralen plus 360-nm radiation assumes a slope of 2. The excision-repair-defective strain is considerably more sensitive to the furocoumarins plus 360-nm radiation than is the radiation-insensitive strain, both for killing and mutation induction. The simplest explanation for the data is that both cross-links and monoadducts, formed by furocoumarins with DNA when exposed to 360-nm radiation, are capable of inducing mutations, and that monoadducts are repaired 20 times more efficiently than cross-links by the excision-repair pathway.

DNA Repair↗

PubMed1976

Role of post-replication and excision repair mechanism in the induction of Trp+ revertants of UV-irradiated Escherichia coli.

Both the post-replication and the excision repair mechanism participate in the induction of Trp+ revertants in Escherichia coli B/r Hcr+ thy trp after a UV-irradiation. At low radiation doses (surviving cell fraction greater than 10(-1) most Trp+ reversions are due to post-replication repair mechanism while at high doses (surviving cell fraction less than 10(-1)) the Trp+ reversions arise probably as the result of an inaccurate excision repair. The absolute accuracy of repair processes decreases with increasing radiation dose.

DNA Repair↗