• Title/Summary/Keyword: Nucleotide excision repair

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The DNA Repair Gene ERCC6 rs1917799 Polymorphism is Associated with Gastric Cancer Risk in Chinese

  • Liu, Jing-Wei;He, Cai-Yun;Sun, Li-Ping;Xu, Qian;Xing, Cheng-Zhong;Yuan, Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.6103-6108
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    • 2013
  • Objective: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotide excision repair pathway that plays an important role in maintaining genomic stability and integrity. Several recent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, the relation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex- and age-matched case-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the association between a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk. Methods: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status of Helicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95% confidential interval (CI) were calculated by logistic regression analysis. Results: Compared with the common TT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46, 95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrated a statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was also observed for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs. T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to be enhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reach statistical significance. Conclusions: ERCC6 rs1917799 GG genotype might be associated with increased GC risk in Chinese, especially in males.

Complete genome sequence of Spirosoma montaniterrae DY10T isolated from gamma-ray irradiated soil (감마선 조사된 토양에서 분리된 박테리아 Spirosoma montaniterrae DY10T 의 완전한 게놈 서열)

  • Srinivasan, Sathiyaraj;Kang, Myung-Suk;Kim, Myung Kyum
    • Korean Journal of Microbiology
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    • v.53 no.1
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    • pp.61-63
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    • 2017
  • A Gram-negative, yellow-pigmented, long-rod shaped bacterium Spirosoma montaniterrae $DY10^T$ was isolated from a soil sample collected at Mt. Deogyusan, Jeonbuk Province, Republic of Korea. Cells showed extreme gamma radiation resistance with the $D_{10}$ value of 12 KGy. The complete genome sequence of strain $DY10^T$ is consist of a circular chromosome (5,797,678 bp) encoding 5,116 genes, 9 rRNA genes and 39 tRNA genes. The genomic features contain the key enzymes for gamma and UVC radiation.

Binding Pattern Elucidation of NNK and NNAL Cigarette Smoke Carcinogens with NER Pathway Enzymes: an Onco-Informatics Study

  • Jamal, Qazi Mohammad Sajid;Dhasmana, Anupam;Lohani, Mohtashim;Firdaus, Sumbul;Ansari, Md Yousuf;Sahoo, Ganesh Chandra;Haque, Shafiul
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5311-5317
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    • 2015
  • Cigarette smoke derivatives like NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol) are well-known carcinogens. We analyzed the interaction of enzymes involved in the NER (nucleotide excision repair) pathway with ligands (NNK and NNAL). Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. The highest obtained docking energy between NNK and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.13 kcal/mol, -7.27 kcal/mol, -8.05 kcal/mol and -7.58 kcal/mol respectively. Similarly the highest obtained docking energy between NNAL and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.46 kcal/mol, -7.94 kcal/mol, -7.83 kcal/mol and -7.67 kcal/mol respectively. In order to find out the effect of NNK and NNAL on enzymes involved in the NER pathway applying protein-protein interaction and protein-complex (i.e. enzymes docked with NNK/NNAL) interaction analysis. It was found that carcinogens are well capable to reduce the normal functioning of genes like RAD23A (HR23A), CCNH, CDK7 and CETN2. In silico analysis indicated loss of functions of these genes and their corresponding enzymes, which possibly might be a cause for alteration of DNA repair pathways leading to damage buildup and finally contributing to cancer formation.

Comprehensive Assessment of Associations between ERCC2 Lys751Gln/Asp312Asn Polymorphisms and Risk of Non-Hodgkin Lymphoma

  • Zhou, Jue-Yu;He, Li-Wen;Liu, Jie;Yu, Hai-Lang;Wei, Min;Ma, Wen-Li;Shi, Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9347-9353
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    • 2014
  • Background: Excision repair crossing-complementing group 2 (ERCC2), also called xeroderma pigmentosum complementary group D (XPD), plays a crucial role in the nucleotide excision repair (NER) pathway. Previous epidemiological studies have reported associations between ERCC2 polymorphisms and non-Hodgkin lymphoma (NHL) risk, but the results have remained controversial. Materials and Methods: We conducted this meta-analysis based on eligible case-control studies to investigate the role of two ERCC2 polymorphisms (Lys751Gln and Asp312Asn) in determining susceptibility to NHL. Ten case-control studies from several electronic databases were included in our study up to August 14, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models to estimate the association strength. Results: The combined results based on all studies did not show any association between Lys751Gln/Asp312Asn polymorphisms and NHL risk for all genetic models. Stratified analyses by histological subtype and ethnicity did not indicate any significant association between Lys751Gln polymorphism and NHL risk. However, a significant reduced risk of NHL was found among population-based studies (Lys/Gln versus Lys/Lys: OR=0.87, 95% CI=0.77-0.99, P=0.037) but not hospital-based studies. As for Asp312Asn polymorphism, there was no evidence for the association between this polymorphism and the risk of NHL in all subgroup analyses. Conclusions: This meta-analysis suggests that there may be no association between Lys751Gln/Asp312Asn polymorphism and the risk of NHL and its two subtypes, whereas ERCC2 Lys751Gln heterozygote genotype may provide protective effects against the risk of NHL in population-based studies. Therefore, large-scale and well-designed studies are needed to clarify the effects of haplotypes, gene-gene, and gene-environment interactions on these polymorphisms and the risk of NHL and its different histological subtypes in an ethnicity specific population.

Study on Expression and Characterization of HRD3 Gene Related DNA Repair from Eukaryotic Cells (진핵세포에서 DNA 회복에 관련된 HRD3 유전자의 분리, 발현 및 특성 연구)

  • Shin, Su-Hwa;Park, In-Soon
    • Journal of Life Science
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    • v.14 no.2
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    • pp.325-330
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    • 2004
  • The RAD3 gene of Saccharomyces cerevisiae is required for excision repair and is essential for cell viability. 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 RAD3 during eukaryotic evolution, the RAD3 homolog gene was isolated by screening of genomic DNA library. The isolated gene was designated as HRD3 (Homologue of RAD3 gene). The over-expressed HRD3 protein was estimated to be a 75 kDa in size which is in good agreement with the estimated by the nucleotide sequence of the cloned gene. Two-dimensional gel electrophoresis showed that a number of other protein spots dramatically disappeared when the HRD3 protein was overexpressed. The overexpressed RAD3 protein showed a toxicity in E. coli host, suggesting that this protein may be involved in the inhibition of protein synthesis and/or degradation of host protein. To determine which part of HRD3 gene contributes to the toxicity in E. coli, various fusion plasmids containing a partial sequence of HRD3 and lac'Z gene were constructed. These results suggest that the C-terminal domain of HRD3 protein may be important for both toxic effect in E. coli and for its role in DNA repair in S. pombe.

Complete genome sequence of Deinococcus puniceus DY1T, a radiation resistant bacterium (방사선 내성 세균 Deinococcus puniceus DY1T의 완전한 게놈 서열 분석)

  • Srinivasan, Sathiyaraj;Sohn, Eun-Hwa;Jung, Hee-Young;Kim, Myung Kyum
    • Korean Journal of Microbiology
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    • v.54 no.1
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    • pp.84-86
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    • 2018
  • Cells of Deinococcus puniceus $DY1^T$ are Gram-positive, coccus-shaped, and crimson color-pigmented. Strain $DY1^T$ was isolated from soil irradiated with 5 kGy gamma radiation and showed resistance to UVC and gamma radiation. In this study, we report the complete genome sequence of a bacterium Deinococcus puniceus $DY1^T$ is consist of circular chromosome comprised of 2,971,983 bp, with the G + C content of 62.5%. The complete genome sequence was obtained using the PacBio RS II platform, it included 2,617 coding sequences (CDs), 2,762 genes, and 88 pseudogene.

Complete genome sequence of Flavisolibacter tropicus LCS9T, a radiation resistant bacterium (방사선 내성 세균 Flavisolibacter tropicus LCS9T의 완전한 게놈 서열)

  • Kim, Myung Kyum;Sohn, Eun-Hwa;Jung, Hee-Young;Srinivasan, Sathiyaraj
    • Korean Journal of Microbiology
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    • v.54 no.1
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    • pp.87-89
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    • 2018
  • Flavisolibacter tropicus $LCS9^T$ was isolated from a soil sample collected from tropical zone within the Ecorium of the National Institute of Ecology in Seocheon, central-western Korea. In this study, we report the complete genome sequence of the bacterium Flavisolibacter tropicus $LCS9^T$, which possesses a circular chromosome comprised of 5, 940,863 bp with the G + C mol content of 41.5%. The genome sequence annotation showed that the complete genome includes 5,075 genes, 337 pseudogenes, and 59 rRNA genes. The radiation resistance genes such as excinuclease UvrABC complex and UvdE were present in the genome.

Bacillus amyloliquefaciens and Saccharomyces cerevisiae feed supplements improve growth performance and gut mucosal architecture with modulations on cecal microbiota in red-feathered native chickens

  • Lee, Tzu-Tai;Chou, Chung-Hsi;Wang, Chinling;Lu, Hsuan-Ying;Yang, Wen-Yuan
    • Animal Bioscience
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    • v.35 no.6
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    • pp.869-883
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    • 2022
  • Objective: The aim of study was to investigate the effects of in-feed supplementation of Bacillus amyloliquefaciens (BA) and Saccharomyces cerevisiae (SC) on growth performance, gut integrity, and microbiota modulations in red-feathered native chickens (RFCs). Methods: A total of 18,000 RFCs in a commercial farm were evenly assigned into two dietary treatments (control diet; 0.05% BA and 0.05% SC) by randomization and raised for 11 weeks in two separate houses. Fifty RFCs in each group were randomly selected and raised in the original house with the partition for performance evaluations at the age of 9 and 11 weeks. Six non-partitioned RFCs per group were randomly selected for analyses of intestinal architecture and 16S rRNA metagenomics. Results: Feeding BA and SC increased the body weight and body weight gain, significantly at the age of 11 weeks (p<0.05). The villus height/crypt ratio in the small intestines and Firmicutes to Bacteroidetes ratio were also notably increased (p<0.05). The supplementation did not disturb the microbial community structure but promote the featured microbial shifts characterized by the significant increments of Bernesiella, Prevotellaceae_NK3B31_group, and Butyrucimonas, following remarkable decrements of Bacteroides, Rikenellaceae_RC9_gut_group, and Succinatimonas in RFCs with growth benefits. Besides, functional pathways of peptidoglycan biosynthesis, nucleotide excision repair, glycolysis/gluconeogenesis, and aminoacyl transfer ribonucleic acid (tRNA) biosynthesis were significantly promoted (p<0.05). Conclusion: In-feed supplementation of BA and SC enhanced the growth performance, improved mucosal architectures in small intestines, and modulated the cecal microbiota and metabolic pathways in RFCs.

Association of Poly (ADP-Ribose) Polymerase 1 Variants with Oral Squamous Cell Carcinoma Susceptibility in a South Indian Population

  • Anil, Sukumaran;Gopikrishnan, PB;Basheer, Ashik Bin;Vidyullatha, BG;Alogaibi, Yahya A;Chalisserry, Elna P;Javed, Fawad;Dalati, MHN;Vellappally, Sajith;Hashem, Mohamed Ibrahim;Divakar, Darshan Devang
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.4107-4111
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    • 2016
  • Background: Oral cancers account for approximately 2% of all cancers diagnosed each year; however, the vast majority (80%) of the affected individuals are smokers whose risk of developing a lesion is five to nine times greater than that of non-smokers. Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which poly (ADP-ribose) polymerase 1 (PARP-1), plays key roles. Genetic variations in the genes encoding DNA repair enzymes may alter their functions. Several studies reported mixed effects on the association between PARP-1 variants and the risk of cancer development. Till now no reported studies have investigated the association between PARP-1 variants and oral squamous cell carcinoma (OSCC) risk in an Indian population. Materials and Methods: In the present case control study 100 OSCC patients and 100 matched controls were genotyped using PARP1 single nucleotide peptides (SNP's) rs1136410 and rs3219090 using TaqMan assays. Results: The results indicated significantly higher risk with PARP1 rs1136410 minor allele "C" (OR=1.909; p=0.02942; CI, 1.060-3.439). SNP rs1136410 also showed significantly increased risk in patients with smoking habit at C/C genotype and at minor allele C. Conclusions: The PAPR-1 Ala762Val polymorphism may play a role in progression of OSCC. Larger studies with a greater number of samples are needed to verify these findings.

Polymorpshisms of XPC Gene and Risk of Primary Lung Cancer in Koreans (한국인에서 XPC 유전자의 다형성과 원발성 폐암의 위험도)

  • Kim, Kyung-Rock;Lee, Su-Yeon;Choi, Jin-Eun;Kim, Kyung-Mee;Jang, Sang-Soo;Jung, Chi-Young;Kang, Kyung-Hee;Jeon, Kyung-Neoyh;Cha, Sung-Ick;Kim, Chang-Ho;Kam, Sin;Jung, Tae-Hoon;Park, Jae-Yong
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.2
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    • pp.113-126
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    • 2002
  • Background : DNA repair plays a crucial role in protection from cancer-causing agents. Therefore, a reduced DNA repair capacity can increase the susceptibility to lung cancer. The XPC gene contains 15 exons and encodes a 940 amino acid protein that plays a central role in DNA damage recognition of the nucleotide excision repair pathway, which is a major DNA repair mechanisim removing the bulky-helix distorting DNA lesions caused by smoking. Recently several polymorphisms in the XPC gene were identified. In addition, it is possible that these polymorphisms may affect the DNA repair capacity, which modulate cancer susceptibility. The relationship between codon 499 and 939 polymorphisms, and a poly(AT) insertion/deletion polymorphism in the XPC gene, and the lung cancer risk were investigated. Materials and Methods : The genotypes were determined using either PCR or PCR-RFLP analysis in 219 male lung cancer patients and 150 healthy males controls. Results : The frequencies of the genotypes (Val499Ala, PAT and Lys939Gln) among the cases were not significantly different from those of the controls. There was no significant associantion between these polymorphi는 and the lung cancer risk when the analyses were stratified according to age, smoking status and the pack-years of smoking. Moreover, the genotypes had no apparent relationship with any of the histological types of lung cancer. There was a linkage disequilibrium among the Val499Ala, PAT and Lys939Gln polymorphisms. The PAT polymorphism had a strong linkage disequilibrium with the Lys939Gln polymorphism (kappa value=0.87). The XPC haplotypes showed no significant association with the lung cancer risk. Conclusion : These results suggest that XPC Val499Ala, PAT and Lys939Gln polymorphisms are not major contributors to the individual lung cancer susceptibility in Koreans.