• Title/Summary/Keyword: Base excision repair

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Genome-Wide Response of Deinococcus radiodurans on Cadmium Toxicity

  • Joe, Min-Ho;Jung, Sun-Wook;Im, Seong-Hun;Lim, Sang-Yong;Song, Hyun-Pa;Kwon, Oh-Suk;Kim, Dong-Ho
    • Journal of Microbiology and Biotechnology
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    • v.21 no.4
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    • pp.438-447
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    • 2011
  • Deinococcus radiodurans is extremely resistant to various genotoxic conditions and chemicals. In this study, we characterized the effect of a sublethal concentration (100 ${\mu}M$) of cadmium (Cd) on D. radiodurans using a whole-genome DNA microarray. Time-course global gene expression profiling showed that 1,505 genes out of 3,116 total ORFs were differentially expressed more than 2-fold in response to Cd treatment for at least one timepoint. The majority of the upregulated genes are related to iron uptake, cysteine biosynthesis, protein disulfide stress, and various types of DNA repair systems. The enhanced upregulation of genes involved in cysteine biosynthesis and disulfide stress indicate that Cd has a high affinity for sulfur compounds. Provocation of iron deficiency and growth resumption of Cd-treated cells by iron supplementation also indicates that CdS forms in iron-sulfur-containing proteins such as the [Fe-S] cluster. Induction of base excision, mismatch, and recombinational repair systems indicates that various types of DNA damage, especially base excision, were enhanced by Cd. Exposure to sublethal Cd stress reduces the growth rate, and many of the downregulated genes are related to cell growth, including biosynthesis of cell membrane, translation, and transcription. The differential expression of 52 regulatory genes suggests a dynamic operation of complex regulatory networks by Cd-induced stress. These results demonstrate the effect of Cd exposure on D. radiodurans and how the related genes are expressed by this stress.

Polymorphism of the DNA Repair Gene XRCC1 (Arg194Trp) and its role in Colorectal Cancer in Kashmiri Population: a Case Control Study

  • Nissar, Saniya;Sameer, Aga Syed;Rasool, Roohi;Chowdri, Nissar A;Rashid, Fouzia
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6385-6390
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    • 2015
  • Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Materials and Methods: In this study we focused on the Arg194Trp polymorphism of the DNA repair gene XRCC1, involved in base excision repair (BER) and its role in colorectal cancer in Kashmiri population. A case-control study was conducted including 100 cases of colorectal cancer, and 100 hospital-based age- and sex-matched healthy controls to examine the role of XRCC1 genetic polymorphisms in the context of colorectal cancer risk for the Kashmiri population. Results: Genotype analysis of XRCC1 Arg194Trp was conducted with a restriction fragment length polymorphism (RFLP) method. The overall association between the XRCC1 polymorphism and the CRC cases was found to be significant (p < 0.05) with both the heterozygous genotype (Arg/Trp) as well as homozygous variant genotype (Trp/Trp) being moderately associated with the elevated risk for CRC [OR=2.01 (95% CI=1.03-3.94) and OR=5.2(95% CI=1.42-19.5)] respectively. Conclusions: Our results suggest an increased risk for CRC in individuals with XRCC1 Arg194Trp polymorphism suggesting BER repair pathway modulates the risk of developing colorectal cancer in the Kashmiri population.

Exon 8-9 Mutations of DNA Polymerase β in Ovarian Carcinoma Patients from Haldia, India

  • Khanra, Kalyani;Panda, Kakali;Mitra, A.K.;Sarkar, Ranu;Bhattacharya, Chandan;Bhattacharyya, Nandan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4183-4186
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    • 2012
  • Background: Ovarian cancer is the number one killer among all the gynecological cancers. We undertook association study to identify potential alterations in the genomic DNA of a DNA repair gene, DNA polymerase beta ($pol{\beta}$), involved in base excision repair (BER), in ovarian carcinomas of patients from Haldia, India. Mutations, splice variants have been reported earlier in different tumors other than ovarian tumors. Aim: In this study we explored the possibility of association of any mutation of $pol{\beta}$ (Exon 8) with prognosis in 152 ovarian cancer samples. Results: Alteration in the exon 8 region (Exon 8:468, $A{\rightarrow}C$; 15.1%) was noted among fifty seven polymorphism positive samples. Alteration in the intervening sequence 8 (IVS8, -25, $A{\rightarrow}C$; 3.9%) was also noted. All alterations are heterozygous in nature. Conclusions: We found no significant association among the samples from serous type, stage IV, and the $pol{\beta}$ mutations ($P{\leq}0.01$). Only a slight tendency of association was evident between IVS8, -25, A to C; and stage III. Further analysis with a larger number of samples is needed.

Gluteus Maximus Muscle Flap in Tongue in Groove and Wrap Around Pattern for Refractory CSF Leakage in Extradural Cyst Patient

  • Park, Kyong Chan;Lee, Jun Ho;Shim, Jae Jun;Lee, Hyun Ju;Choi, Hwan Jun
    • Archives of Plastic Surgery
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    • v.49 no.3
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    • pp.365-368
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    • 2022
  • Spinal extradural arachnoid cyst (SEAC) is a rare disease and has surgical challenges because of the critical surrounding anatomy. We describe the rare case of a 58-year-old woman who underwent extradural cyst total excision with dural repair and presented with refractory cerebrospinal fluid (CSF) leakage even though two consecutive surgeries including dural defect re-repair and lumbar-peritoneal shunt were performed. The authors covered the sacral defect using bilateral gluteus maximus muscle flap in tongue in groove and wrap around pattern for protection of visible sacral nerve roots and blockage of CSF leakage point. With the flap coverage, the disappearance of cyst and fluid collection was confirmed in the postoperative radiological finding, and the clinical symptoms were significantly improved. By protecting the sacral nerve roots and covering the base of sacral defect, we can minimize the risk of complication and resolve the refractory fluid collection. Our results suggest that the gluteus muscle flap can be a safe and effective option for sacral defect and CSF leakage in extradural cyst or other conditions.

Long Term Follow-Up after Skull Base Reconstrucion (두개저부 종양 절제 및 재건 후 장기 추적관찰)

  • Jin, Ung Sik;Won Minn, Kyung;Heo, Chan Yeong
    • Archives of Plastic Surgery
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    • v.32 no.2
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    • pp.175-182
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    • 2005
  • Skull base tumors have been determined inoperable because it is difficult to accurately diagnose the extent of the involvement and to approach and excise the tumor safely. However, recently, the advent of sophisticated diagnostic tools such as computed tomography and magnetic resonance imaging as well as the craniofacial and neurosurgical advanced techniques enabled an accurate determination of operative plans and safe approach for tumor excision. Resection of these tumors may sometimes result in massive and complex extirpation defects that are not amenable to local tissue closure. The purpose of this study is to analyze experiences of skull base reconstruction and to evaluate long term survival rate and complications. All cranial base reconstructions performed from July 1993 to September 2000 at Department of Plastic and Reconstructive Surgery of the Seoul National University Hospital were observed. The medical records were reviewed and analysed to assess the location of defects, reconstruction method, existence of the dural repair, history of preoperative radiotherapy and chemotherapy, complications and causes of death of the expired patients. There were 12 cases in region II, 8 cases in region I and 1 case in region III according to the Irish classification of skull base. Cranioplasty was performed in 4 patients with a bone graft and microvascular free tissue transfer was selected in 17 patients to reconstruct the cranial base and/or mid-facial defects. Among them, 11 cases were reconstructed with a rectus abdominis musculocutaneous free flap, 2 with a latissimus dorsi muscluocutaneous free flap, 1 with a fibular osteocutaneous free flap, 2 with a scapular osteocutaneous free flap, and 1 with a forearm fasciocutaneous free flap, respectively. During over 3 years follow-up, 5 patients were expired and 8 lesions were relapsed. Infection(3 cases) and partial flap loss(2 cases) were the main complications and multiorgan failure(3 cases) by cancer metastasis and sepsis(2 cases) were causes of death. Statistically 4-years survival rate was 68%. A large complex defects were successfully reconstructed by one-stage operation and, the functional results were also satisfactory with acceptable survival rates.

XRCC3 Thr241Met Gene Polymorphism and Risk of Colorectal Cancer in Kashmir: a Case Control Study

  • Nissar, Saniya;Sameer, Aga Syed;Lone, Tufail A.;Chowdri, Nissar A.;Rasool, Roohi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9621-9625
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    • 2014
  • XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC ($p{\leq}0.05$). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p = 0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.

Association of XRCC1 Gene Polymorphisms with Breast Cancer Susceptibility in Saudi Patients

  • Al Mutairi, Fatima Masoud;Alanazi, Mohammed;Shalaby, Manal;Alabdulkarim, Huda A.;Pathan, Akbar Ali Khan;Parine, Narasimha Reddy
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3809-3813
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    • 2013
  • Background: X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. XRCC1 is reported to be a candidate influence on cancer risk. The aim of our present study was to assess the association of rs1799782 (Arg194Trp) and rs25487 (Arg399Gln) XRCC1 gene polymorphisms with breast cancer in the Saudi population. Materials and Methods: The two SNP's were analyzed in breast cancer patients and healthy control subjects. Genotypes were determined by TaqMan SNP genotype analysis technique and data were analyzed using Chi-square or t test and logistic regression analysis by SPSS16.0 software. Results and Conclusions: Results showed that rs1799782 significantly increased susceptibility to breast cancer with Arg/Trp, Arg/Trp+Trp/Trp genotypes and at Trp allele overall study. It also increased risk of breast cancer in older age patients (above 48) and with the ER positive category. XRCC1rs25487 (Arg399Gln) did not showed any significant association. In conclusion the XRCC1rs1799782 polymorphism may be involved in the etiology of breast cancer in the Saudi population. Confirmation of our findings in larger populations of different ethnicities is warranted.

Association of a Newly Identified Variant of DNA Polymerase Beta (polβΔ63-123, 208-304) with the Risk Factor of Ovarian Carcinoma in India

  • Khanra, Kalyani;Bhattacharya, Chandan;Bhattacharyya, Nandan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1999-2002
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    • 2012
  • Background: DNA polymerase is a single-copy gene that is considered to be part of the DNA repair machinery in mammalian cells. The encoded enzyme is a key to the base excision repair (BER) pathway. It is evident that pol beta has mutations in various cancer samples, but little is known about ovarian cancer. Aim: Identification of any variant form of $pol{\beta}$ cDNA in ovarian carcinoma and determination of association between the polymorphism and ovarian cancer risk in Indian patients. We used 152 samples to isolate and perform RT-PCR and sequencing. Results: A variant of polymerase beta (deletion of exon 4-6 and 11-13, comprising of amino acid 63-123, and 208-304) is detected in heterozygous condition. The product size of this variant is 532 bp while wild type pol beta is 1 kb. Our study of association between the variant and the endometrioid type shows that it is a statistically significant factor for ovarian cancer [OR=31.9 (4.12-246.25) with p<0.001]. The association between variant and stage IV patients further indicated risk (${\chi}^2$ value of 29.7, and OR value 6.77 with 95% CI values 3.3-13.86). The correlation study also confirms the association data (Pearson correlation values for variant/stage IV and variant/endometrioid of 0.44 and 0.39). Conclusion: Individuals from this part of India with this type of variant may be at risk of stage IV, endometrioid type ovarian carcinoma.

The Codon 399 Arg/Gln XRCC1 Polymorphism is Associated with Lung Cancer in Indians

  • Natukula, Kirmani;Jamil, Kaiser;Pingali, Usha Rani;Attili, Venkata Satya Suresh;Madireddy, Umamaheshwar Rao Naidu
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5275-5279
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    • 2013
  • Background: The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility. Materials and Methods: We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed. Results: The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females. Conclusions: It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.