• 제목/요약/키워드: Excision repair

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A Novel UV-Sensitivity Mutation Induces Nucleotide Excision Repair Phenotype and Shows Epistatic Relationships with UvsF and UvsB Groups in Aspergillus nidulans

  • Baptista, F.;Castro-Prado, M.A.A.
    • Journal of Microbiology
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    • 제39권2호
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    • pp.102-108
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    • 2001
  • DNA damage response has a central role in the maintenance of genomic integrity while mutations in related genes may result in a range of disorders including neoplasic formations. The uvsZl characterized in this report is a navel uvs mutation in Aspergillus nidulans, resulting in a nucleotide excision repair (NER) phenotype: UV-sensitivity before DNA synthesis (quiescent cells), high UV-induced mutation frequency and probable absence of involvement with mitotic and meiotic recombinations. The mutation is recessive and nan-allelic to the previously characterized uvsA101 mutation, also located on the paba-y interval on chromosome I. uvsZl skewed wild-type sensitivity to MMS, which suggests non-involvement of this mutation with BER. Epitasis tests showed that the uvsZ gene product is probably involved in the same repair pathways as UVSB or UVSH proteins. Although mutations in these proteins result in an NER phenotype, UVSB is related with cell cycle control and UVSH is associated with the post-replicational repair pathway. The epistatic interaction among uvsZl and uvsB413 and uvsH77 mutations indicates that different repair systems may be related with the common steps of DNA damage response in Aspergillus nidulans.

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Recognition of DNA Damage in Mammals

  • Lee, Suk-Hee
    • BMB Reports
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    • 제34권6호
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    • pp.489-495
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    • 2001
  • DNA damage by UV and environmental agents are the major cause of genomic instability that needs to be repaired, otherwise it give rise to cancer. Accordingly, mammalian cells operate several DNA repair pathways that are not only responsible for identifying various types of DNA damage but also involved in removing DNA damage. In mammals, nucleotide excision repair (NER) machinery is responsible for most, if not all, of the bulky adducts caused by UV and chemical agents. Although most of the proteins involved in NER pathway have been identified, only recently have we begun to gain some insight into the mechanism by which proteins recognize damaged DNA. Binding of Xeroderma pigmentosum group C protein (XPC)-hHR23B complex to damaged DNA is the initial damage recognition step in NER, which leads to the recruitment of XPA and RPA to form a damage recognition complex. Formation of damage recognition complex not only stabilizes low affinity binding of XPA to the damaged DNA, but also induces structural distortion, both of which are likely necessary for the recruitment of TFIIH and two structure-specific endonucleases for dual incision.

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Characterization of HRD3, a Schizosaccharomyces pombe Gene Involved in DNA Repair and Cell Viability

  • Choi, In-Soon
    • Animal cells and systems
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    • 제7권2호
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    • pp.159-164
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    • 2003
  • The RAD3 gene of Saccharomyces cerevisiae is required for excision repair and is essential for cell viability. The RAD3 encoded protein possesses a single stranded DNA-dependent ATPase and DNA and DNA-RNA helicase activities. To examine the extent of conservation of structure and function of a S. pombe RAD3 during eukaryotic evolution, the RAD3 homolog gene was isolated by screening of genomic DNA library. The isolated gene was designated as HRD3 (homolog of RAD3 gene). Southern blot analysis confirmed that S. pombe chromosome contains the same DNA as HRD3 gene and this gene exists as a single copy in S. pombe. The transcript of 2.8 kb was detected by Northern blot analysis, The level of transcripts increased by ultraviolet (UV) irradiation, indicating that HRD3 is one of the UV-inducible genes in S. pombe. Furthermore, the predicted partial sequence of HRD3 protein has 60% identity to S. cerevisiae RAD3 gene. This homology was particularly striking in the regions identified as being conserved in a group of DNA helicases. Gene deletion experiments indicate that the HRD3 gene is essential for viability and DNA repair function. These observations suggest evolutionary conservation of other protein components with which HRD3 might interact in mediating its DNA repair and viability functions.

Photoprotection by Topical DNA Repair Enzymes

  • Yarosh, Daniel B.
    • Journal of Photoscience
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    • 제9권2호
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    • pp.186-189
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    • 2002
  • Many of the adverse effects of solar UV exposure appear to be directly attributable to damage to epidermal DNA. In particular, cyclobutane pyrimidine dimers (CPD) may initiate mutagenic changes as well as induce signal transduction responses that lead to a loss of skin immune surveillance and micro-destruction of skin structure. Our approach is to reverse the DNA damage using prokaryotic DNA repair enzymes delivered into skin using specially engineered liposomes. T4 endonuclease V encapsulated in liposomes (T4N5 liposome lotion) enhanced DNA repair by shifting repair of CPD from the nucleotide excision to the base excision repair pathway. Following topical application to humans, increased repair limited UV-induction of cytokines, many of which are immunosuppressive. In a recent clinical study, topical treatment of UV-irradiated human skin with T4N5 liposome lotion reduced the suppression of the nickel sulfate contact hypersensitivity response. Similarly, the photoreactivating enzyme enhances repair by directly reversing CPDs after absorbing activating light. Here also treatment of UV-irradiated human skin with photoreactivating enzyme in liposomes and photoreactivating light restored the response to the contact allergen nickel sulfate. These findings confirm in humans the observation in mice that UV induced suppression of contact hypersensitivity is caused in part by CPDs. We have tested the ability of T4N5 liposome lotion to prevent UV-induced skin cancer in patients with xeroderma pigmentosum (XP), who have an elevated incidence of skin cancer resulting from a genetic defect in DNA repair. Daily use of the lotion for one year in a group of 20 XP patients reduced the average number of actinic keratoses by 68% and basal cell cancers by 30% compared to 9 patients in the placebo control group. Delivery of DNA repair enzymes to skin is a promising new approach to photoprotection.

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Influence of Morinda citrifolia (Noni) on Expression of DNA Repair Genes in Cervical Cancer Cells

  • Gupta, Rakesh Kumar;Bajpai, Deepti;Singh, Neeta
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권8호
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    • pp.3457-3461
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    • 2015
  • Background: Previous studies have suggested that Morinda citrifolia (Noni) has potential to reduce cancer risk. Objective: The purpose of this study was to investigate the effect of Noni, cisplatin, and their combination on DNA repair genes in the SiHa cervical cancer cell line. Materials and Methods: SiHa cells were cultured and treated with 10% Noni, $10{\mu}g/dl$ cisplatin or their combination for 24 hours. Post culturing, the cells were pelleted, RNA extracted, and processed for investigating DNA repair genes by real time PCR. Results: The expression of nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and base excision repair gene XRCC1 was increased 4 fold, 8.9 fold, 4 fold, and 5.5 fold, respectively, on treatment with Noni as compared to untreated controls (p<0.05). In contrast, expression was found to be decreased 22 fold, 13 fold, 16 fold, and 23 fold on treatment with cisplatin (p<0.05). However, the combination of Noni and cisplatin led to an increase of 2 fold, 1.6 fold, 3 fold, 1.2 fold, respectively (p<0.05). Conclusions: Noni enhanced the expression of DNA repair genes by itself and in combination with cisplatin. However, high expression of DNA repair genes at mRNA level only signifies efficient DNA transcription of the above mentioned genes; further investigations are needed to evaluate the DNA repair protein expression.

Reconstruction Techniques for Tissue Defects Formed after Preauricular Sinus Excision

  • Lee, Myung Joon;Yang, Ho Jik;Kim, Jong Hwan
    • Archives of Plastic Surgery
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    • 제41권1호
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    • pp.45-49
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    • 2014
  • Background Preauricular sinuses are congenital abnormalities caused by a failure of fusion of the primitive tubercles from which the pinna is formed. When persistent or recurring inflammation occurs, surgical excision of the infected tissue should be considered. Preauricular defects inevitably occur as a result of excisions and are often difficult to resolve with a simple suture; a more effective reconstruction technique is required for treating these defects. Methods After total excision of a preauricular sinus, the defect was closed by a plastic surgeon. Based on the depth of the defect and the degree of tension when apposing the wound margins, the surgeon determined whether to use primary closure or a posterior auricular flap. Results A total of 28 cases were examined. In 5 cases, including 2 reoperations for dehiscence after primary repair, reconstruction was performed using posterior auricular transposition flaps. In 16 cases of primary closure, the defects were closed using simple sutures, and in 7 cases, closure was performed after wide undermining. Conclusions If a preauricular defect is limited to the subcutaneous layer and the margins can be easily approximated, primary closure by only simple suturing may be used to perform the repair. If the defect is deep enough to expose the perichondrium or if there is tension when apposing the wound margins, wide undermining should be performed before primary closure. If the extent of the excision exposes cartilage, the procedure follows dehiscence of the primary repair, or the tissue is not sufficiently healthy, the surgeon should use a posterior auricular flap.

Multidirectional Vector Excision Leads to Better Outcomes than Traditional Elliptical Excision of Facial Congenital Melanocytic Nevus

  • Oh, Seung Il;Lee, Yoon Ho
    • Archives of Plastic Surgery
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    • 제40권5호
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    • pp.570-574
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    • 2013
  • Background The elliptical excision is the standard method of removing benign skin lesions, such as congenital melanocytic nevi. This technique allows for primary closure, with little to no dog-ear deformity, but may sacrifice normal tissue adjacent to the lesion, resulting in scars which are unnecessarily long. This study was designed to compare the predicted results of elliptical excision with those resulting from our excision technique. Methods Eighty-two patients with congenital melanocytic nevus on the face were prospectively studied. Each lesion was examined and an optimal ellipse was designed and marked on the skin. After an incision on one side of the nevus margin, subcutaneous undermining was performed in the appropriate direction. The skin flap was pulled up and approximated along several vectors to minimize the occurrence of dog-ear deformity. Results Overall, the final wound length was 21.1% shorter than that achieved by elliptical excision. Only 8.5% of the patients required dog-ear repair. There was no significant distortion of critical facial structures. All of the scars were deemed aesthetically acceptable based on their Patient and Observer Scar Assessment Scale scores. Conclusions When compared to elliptical excision, our technique appears to minimize dogear deformity and decrease the final wound length. This technique should be considered an alternative method for excision of facial nevi.

Comparison of complete surgical excision and minimally invasive excision using CO2 laser for removal of epidermal cysts on the face

  • Kim, Keun Tae;Sun, Hook;Chung, Eui Han
    • 대한두개안면성형외과학회지
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    • 제20권2호
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    • pp.84-88
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    • 2019
  • Background: Epidermal cysts are benign, slow growing cysts that often develop on the head, neck, chest, and back of adults. The most common method of surgical excision involves the use of a scalpel and often leaves a scar proportional to the size of the cyst. Therefore, minimally invasive techniques are required. Among these techniques, the $CO_2$ laser-based technique is minimally invasive and has lower complication rate, shorter recovery times, and lesser scarring. This paper aimed to compare the results and postoperative complications associated with a $CO_2$ laser-based excision against conventional surgical excision for epidermal cysts. Methods: We surveyed 120 patients, aged 16 to 65 years, with epidermal cysts on the face measuring 0.5 to 2.2 cm in diameter. Twelve months later, we compared the scar length, recurrence rate, patient satisfaction, and complications between patients treated with $CO_2$ laser excision versus surgical excision. Results: The mean scar length (12 months postoperative) after $CO_2$ laser excision was $0.30{\pm}0.15cm$, and that following surgical excision was $1.23{\pm}0.43cm$ (p= 0.001). The procedure time (time from incision after local anesthesia to the end of repair) was $16.15{\pm}5.96minutes$ for $CO_2$ laser excision versus $22.38{\pm}6.05minutes$ for surgical excision (p= 0.001). The recurrence rates in the surgical excision group and $CO_2$ laser excision group were 3.3% and 8.3%, respectively; this difference was not statistically significant (p= 0.648). Conclusion: The cosmetic outcome of $CO_2$ laser excision is excellent. For epidermal cysts measuring 2.2 cm or smaller, $CO_2$ laser excision is recommended, especially when aesthetic outcome is considered important.

Association of DNA Base-excision Repair XRCC1, OGG1 and APE1 Gene Polymorphisms with Nasopharyngeal Carcinoma Susceptibility in a Chinese Population

  • Li, Qing;Wang, Jian-Min;Peng, Yu;Zhang, Shi-Heng;Ren, Tao;Luo, Hao;Cheng, Yi;Wang, Dong
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권9호
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    • pp.5145-5151
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    • 2013
  • Background: Numerous carcinogens and reactive oxygen species (ROS) may cause DNA damage including oxidative base lesions that lead to risk of nasopharyngeal carcinoma. Genetic susceptibility has been reported to play a key role in the development of this disease. The base excision repair (BER) pathway can effectively remove oxidative lesions, maintaining genomic stability and normal expression, with X-ray repair crosscomplementing1 (XRCC1), 8-oxoguanine glycosylase-1 (OGG1) and apurinic/apyimidinic endonuclease 1 (APE1) playing important roles. Aims: To analyze polymorphisms of DNA BER genes (OOG1, XRCC1 and APE1) and explore their associations, and the combined effects of these variants, with risk of nasopharyngeal carcinoma. Materials and Methods: We detected SNPs of XRCC1 (Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu and -141T/G) using the polymerase chain reaction (PCR) with peripheral blood samples from 231 patients with NPC and 300 healthy people, furtherly analyzing their relations with the risk of NPC in multivariate logistic regression models. Results: After adjustment for sex and age, individuals with the XRCC1 399Gln/Gln (OR=1.96; 95%CI:1.02-3.78; p=0.04) and Arg/Gln (OR=1.87; 95%CI:1.29-2.71; p=0.001) genotype variants demonstrated a significantly increased risk of nasopharyngeal carcinoma compared with those having the wild-type Arg/Arg genotype. APE1-141G/G was associated with a significantly reduced risk of NPC (OR=0.40;95%CI:0.18-0.89) in the smoking group. The OR calculated for the combination of XRCC1 399Gln and APE1 148Gln, two homozygous variants, was significantly additive for all cases (OR=2.09; 95% CI: 1.27-3.47; p=0.004). Conclusion: This is the first study to focus on the association between DNA base-excision repair genes (XRCC1, OGG1 and APE1) polymorphism and NPC risk. The XRCC1 Arg399Gln variant genotype is associated with an increased risk of NPC. APE1-141G/G may decrease risk of NPC in current smokers. The combined effects of polymorphisms within BER genes of XRCC1 399Gln and APE1 148Gln may contribute to a high risk of nasopharyngeal carcinoma.

견관절 전방 관절과 순 파열을 동반한 관절와 순 낭종 - 1례 보고- (Glenoid Labral Cyst with Anterior Labral Tear in the Shoulder - A Case Report -)

  • 김영규;송민호
    • Clinics in Shoulder and Elbow
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    • 제3권1호
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    • pp.49-53
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    • 2000
  • There are few case reports of glenoid labral cysts related to the labral tear in the shoulder. Glenoid labral cyst is often overlooked in the diagnosis of shoulder pain. We are reporting a case of a glenoid labral cyst accompanying with anterior labral tear in the right shoulder of a 42 years old woman with the history of trauma. The cyst and anterior labral tear was successfully treated with arthroscopic excision and repair.

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