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Cross-linking of 2-deoxyribonolactone and its beta-elimination product by base excision repair enzymes.

2-Deoxyribonolactone (3) is produced in DNA as a result of reaction with a variety of DNA damaging agents. The lesion undergoes beta-elimination to form a second metastable electrophilic product (4). In this study, DNA containing 2-deoxyribonolactone (3) and its beta-elimination product (4) are generated at specific sites using a photolabile nucleotide precursor. 2-Deoxyribonolactone is not incised by any of the 8 AP lyases tested. One enzyme, Escherichia coli endonuclease III, cross-links to 3, and the lesion strongly inhibits excision of typical abasic sites by this enzyme. Two of the enzyme

Critical DNA damage recognition functions of XPC-hHR23B and XPA-RPA in nucleotide excision repair.

It has been reported that 80-90% of human cancers may result, in part, from DNA damage. Cell survival depends critically on the stability of our DNA and exquisitely sensitive DNA repair mechanisms have developed as a result. In humans, nucleotide excision repair (NER) protects the DNA against the mutagenic effects of carcinogens and ultraviolet (UV) radiation from sun exposure. By preventing mutations from forming in the DNA, the repair machinery ultimately protects us from developing cancers. DNA damage recognition is the rate-limiting step in repair, and although many details of NER have bee…

Drosophila MUS312 interacts with the nucleotide excision repair endonuclease MEI-9 to generate meiotic crossovers.

MEI-9 is the Drosophila homolog of the human structure-specific DNA endonuclease XPF. Like XPF, MEI-9 functions in nucleotide excision repair and interstrand crosslink repair. MEI-9 is also required to generate meiotic crossovers, in a function thought to be associated with resolution of Holliday junction intermediates. We report here the identification of MUS312, a protein that physically interacts with MEI-9. We show that mutations in mus312 elicit a meiotic phenotype identical to that of mei-9 mutants. A missense mutation in mei-9 that disrupts the MEI-9-MUS312 interaction abolishes the mei…

Triple-helix formation induces recombination in mammalian cells via a nucleotide excision repair-dependent pathway.

The ability to stimulate recombination in a site-specific manner in mammalian cells may provide a useful tool for gene knockout and a valuab … is capable of promoting recombination and that this effect is dependent on a functional nucleotide excision repair (NER) pathway. Transfection of COS cells carrying the dual supF vector with a purine-rich TFO, AG30, designed to bind as a third strand to a region between the two mutant supF genes yielded recombinants at a frequency of 0.37%, fivefold above backgr …

Expression and nucleotide excision repair of a UV-irradiated reporter gene in unirradiated human cells.

It has been suggested that reactivation of damaged reporter genes introduced into cultured mammalian cells reflects transcription-coupled nucleotide excision repair. To evaluate this possibility directly, we introduced a UV-irradiated shuttle vector, pCMV beta, into unirradiated human cells and compared expression of the reporter gene (lacZ) with repair of cyclobutane pyrimidine dimers (CPDs). Expression of the irradiated reporter gene was more UV resistant in XPC cells, which are deficient in global genome repair, than in CSB cells, which are deficient in transcription-coupled repair. These r…

Role of excision repair in UVB-induced depletion and recovery of human epidermal Langerhans cells.

Skin exposure to UVB radiation deprives the antigen-presenting function and OKT6 monoclonal antibody-binding characteristics of Langerhans cells. Decrease of Langerhans cell population could be relevant to immune surveillance disturbance in the UV-exposed skin. Patients with xeroderma pigmentosum exhibit a thousandfold higher risk for sunlight-induced skin cancers than patients with normal skin, and also have various defects in cellular immunity. Therefore, studies of numerical and structural changes in epidermal Langerhans cells of patients with xeroderma pigmentosum after UVB irradiation com

Perineal excision of rectal prolapse with posterior levator ani repair in elderly high-risk patients.

Perineal excision of rectal prolapse with simultaneous posterior levator ani repair was used to treat 41 elderly patients with rectal procidentia. The majority of the patients had significant associated risk factors. This procedure was performed with minimal morbidity and no mortality. A significant improvement in anal continence was seen in 78 percent of patients. The recurrence rate of rectal prolapse was 4.8 percent.

The interaction of XPG with TFIIH through p62 and XPD is required for the completion of nucleotide excision repair.

Nucleotide excision repair (NER) is the key pathway for the removal of DNA damage induced by UV irradiation and chemotherapeutic reagents. Protein-protein interactions are crucial for the dynamic and coordinated assembly of the proteins involved in DNA lesions. Here we focus on the role of interactions between the multi-subunit helicase/translocase complex TFIIH and the 3' endonuclease XPG. We show that XPG interacts with the p62 and XPD subunits of TFIIH through its long spacer region bridging its split active site. We show that interactions between three acidic regions of XPG and the Pleckst…

Minimally Invasive Surgery for the Excision and Repair of Cesarean Scar Defect: A Scoping Review of the Literature.

Background and Objectives: The isthmocele is a pouch-shaped defect in the anterior uterine wall, site of a previous cesarean section, due to a scar defect or dehiscence. The prevalence could be underestimated, but the rate of cesarean section is still high in the world. The preferable technique to correct this anomaly is not clearly indicated in the literature. Our objective is to evaluate the literature on the surgical treatment of isthmocele in pre-Cesarean women treated with minimally invasive technique. Our hypothesis is that robotic treatment is more effective than other procedures in wom

Laparoscopic excision and repair of a cesarean scar pregnancy in a woman with uterine didelphys: a case report.

Cesarean scar pregnancy (CSP) is a rare complication that occurs in less than 1% of ectopic pregnancies, and uterine didelphys is one of the rarest uterine forms. We report a successful laparoscopic excision and repair of CSP in a woman with uterine didelphys and a double vagina. A 34-year-old gravida one, para one woman with a history of low transverse cesarean section presented to our hospital with a suspected CSP. She was confirmed to have uterine didelphys with a double vagina during an infertility examination 7 years earlier. Magnetic resonance imaging showed a 2.5-cm gestational sac-like

A further definition of characteristics of DNA-excision repair in xeroderma pigmentosum complementation group A strains.

The location in the genome of excision repair following exposure to UV (254 nm) of two XP complementation group A strains, XP12BE and XP8LO, that differ considerably in their excision-repair rates, have been determined. Capacity for repair in XP8LO has also been determined. Sites repaired in DNA in a 24-h post-UV period were located relative to the remaining pyrimidine dimers using the M. luteus UV-endonuclease to nick partially repaired DNA and sedimentation in alkaline sucrose to size the resulting DNA. Repair in group A occurs randomly throughout the genome in a manner similar to that obser…

Окисляющая ДНК Повреждение и Ремонт Динамики Множественного Склероза: Отчёты от кометы Ассей Кинетика, Ремонт Гены и Генотипный анализ.

Множественный склероз (MS) — нервно-воспалительное заболевание, при котором окислительный стресс и повреждения ДНК могут влиять на прогрессию болезни. Мы изучили вопрос о том, способствуют ли дефекты в проведении операций по обрезанию оснований (BER) MS благодаря сочетанию функциональных анализов по ремонту ДНК, профилирования экспрессии генов и анализа генотипов. Мы собрали периферийные кровеносные моноядерные клетки у 70 пациентов MS и 61 здоровый контроль. Эти клетки подвергались воздействию окислительного стресса, вызванного терт-бутилом гидропероксидом (ТБГ), и за 60 минут были измерены к

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a neuroinflammatory disease where oxidative stress and DNA damage may influence disease progression. We investigated whether defects in base excision repair (BER) pathways contribute to MS by combining functional DNA repair assays, gene expression profiling, and genotype analysis. We collected peripheral blood mononuclear cells fro…

Cell cycle checkpoint abrogator UCN-01 inhibits DNA repair: association with attenuation of the interaction of XPA and ERCC1 nucleotide excision repair proteins.

UCN-01, an anticancer agent currently in Phase I clinical trials, has been found to potentiate the cytotoxicity of cisplatin (CDDP). Because mammalian cells remove CDDP-induced DNA adducts through the nucleotide excision repair (NER) pathway, we determined the effects of UCN-01 on NER by measuring its effects on the interaction of the repair factors XPA and ERCC1 and the phosphorylation/dephosphorylation of the repair proteins. The repair activity, as measured by an in vitro repair synthesis assay and an in vivo host-cell reactivation assay using A549 cells, was significantly reduced. Although…

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 … 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 …

Arid1a Deficiency Drives Aristolochic Acid-Induced Liver Tumorigenesis through Ctnnb1 Mutation and Defective Nucleotide Excision Repair.

ARID1A, which encodes an important subunit of SWI/SNF complex, is frequently mutated in non-malignant tissues and tumors. However, how ARID1 … rid1a deficiency transcriptionally represses the expression of critical genes related to nucleotide excision repair, which removes AAI-derived DNA adducts, due to SWI/SNF complex dysfunction. Simultaneously, it upregulates Nqo1, a key enzyme enhancing AAI bioactivation and AAI-DNA adduct formation. This dual-hit mechanism, characterized by impaired DNA repair and …

Cancer-associated fibroblast derived CXCL14 drives cisplatin chemoresistance by enhancing nucleotide excision repair in bladder cancer.

BACKGROUND: A significant challenge in bladder cancer treatment is primary chemoresistance, in which cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a pivotal role. While the contributions of CAFs to tumor progression and drug resistance are well established, the precise molecular mechanisms by which they induce chemoresistance remain unclear. A comprehensive understanding of the effect of TME modulation-particularly through CAFs-on the chemotherapeutic response is crucial for developing effective strategies to overcome chemoresistance and improve patient survival

DNA N-glycosylases Ogg1 and EndoIII as components of base excision repair in Plasmodium falciparum organelles.

The integrity of genomes of the two crucial organelles of the malaria parasite - an apicoplast and mitochondrion in each cell - must be maintained by DNA repair mediated by proteins targeted to these compartments. We explored the localisation and function of Plasmodium falciparum base excision repair (BER) DNA N-glycosylase homologs PfEndoIII and PfOgg1. These N-glycosylases would putatively recognise DNA lesions prior to the action of apurinic/apyrimidinic (AP)-endonucleases. Both Ape1 and Apn1 endonucleases have earlier been shown to function solely in the parasite mitochondrion. Immunofluor…

Genome instability independent of type I interferon signaling drives neuropathology caused by impaired ribonucleotide excision repair.

Aicardi-Goutières syndrome (AGS) is a monogenic type I interferonopathy characterized by neurodevelopmental defects and upregulation of type I interferon signaling and neuroinflammation. Mutations in genes that function in nucleic acid metabolism, including RNASEH2, are linked to AGS. Ribonuclease H2 (RNASEH2) is a genome surveillance factor critical for DNA integrity by removing ribonucleotides incorporated into replicating DNA. Here we show that RNASEH2 is necessary for neurogenesis and to avoid activation of interferon-responsive genes and neuroinflammation. Cerebellar defects after RNASEH2