• 제목/요약/키워드: DNA repair genes

검색결과 154건 처리시간 0.032초

Implication of Polymorphisms in DNA Repair Genes in Prognosis of Hepatocellular Carcinoma

  • Yue, Ai-Min;Xie, Zhen-Bin;Guo, Shu-Ping;Wei, Qi-Dong;Yang, Xiao-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권1호
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    • pp.355-358
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    • 2013
  • XRCC1 genetic polymorphisms could be associated with increased risk of various cancer, including hepatocellular carcinoma (HCC), the fifth most common cancer. We here conducted a study to explore the role of selective SNPs of the XRCC1 and XPD genes in the prognosis of HCC. A total of 231 cases were collected, and genotyping of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XPD Lys751Gln and XPD Asp312Asn was performed by duplex polymerase-chain-reaction with the confronting-two-pair primer method. Our findings indicated XRCC1 399Gln/Gln genotype was associated with a significant difference in the median survival time compared with patients carrying Arg/Trp and Arg/Arg genotypes, and individuals with XPD 751 Gln/ Gln genotype had a significantly greater survival time than patients carrying Lys/Lys and Lys/Gln genotypes. The Cox's regression analysis showed individuals carrying XRCC1 399Trp/Trp genotype had 0.55 fold risk of death from HCC than Arg/Arg genotype. Similarly, XPD 751Gln/Gln had a strong decreasein comparison to XPD Lys/Lys carriers with an HR of 0.34. These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in the prognosis of HCC.

Antioxidant Activity and Its Mechanism of Paeonia lactiflora Pall Extract

  • Heo, Jee-In;Kim, Jeong-Hyeon;Lee, Jeong-Min;Kim, Sung-Chan;Park, Jae-Bong;Kim, Jaebong;Lee, Jae-Yong
    • Natural Product Sciences
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    • 제19권1호
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    • pp.49-53
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    • 2013
  • Paeonia lactiflora Pall (PL) has been used as a traditional herbal medicine in China, Korea, and Japan for more 1,200 years. PL has reported to have antioxidant activity and protective effect of cells from oxidative stress, although the mechanism has not been verified. FOXO3a is a transcription factor that binds to its target gene's consensus FOXO binding site. FOXO3a protein modulates the various biological functions including cell cycle control, apoptosis, DNA repair, and ROS detoxification. Therefore, FOXO3a activity is associated with cancer, aging, diabetes, infertility, neurodegeneration, and immune system dysfunction. Here we found that FOXO3a was activated by PL extract. Transcriptional target genes such as MnSOD, p27, and GADD45 were activated by PL extract. Protein levels of MnSOD and catalase were increased, consequently, ROS level was reduced in HEF cells by PL extract. These findings suggest that PL extract has an antioxidant activity through FOXO activation and thereby activation of FOXO target genes, MnSOD and catalase.

Aspergillus nidulans의 자외선 감수성, uvs 돌연변이주들의 epistatic 연관성 및 성질에 대하여 (Analysis of epistatic interactions and properties of UV-sensitive, uvs mutants of Aspergillus nidulans)

  • 채순기
    • 자연과학논문집
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    • 제11권1호
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    • pp.45-54
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    • 1999
  • 4-NQO에 대한 감수성을 이용한 A.nidulans uvs 유전자들의 epistatic grouping은 자외선 및 MMS의 감수성을 이용한 grouping과 동일한 결과를 보였다. 한편, MMS에 대한 감수성을 기준으로 분류한 epistasis group에서 uvsA는 UvsF group 유전자인 uvsF 및 uvsH와 synergistic interaction을 보였으며, uvsA;uvsB 및 uvsA;uvsC 이배체는 uvsB, uvsC의 반수체와 동일한 감수성을 나타내었다. Germination한 뒤 4시간 후의 자외선 감수성을 기준으로 한 uvsI의 epistatic grouping은 conidia 상태에서 자외선을 쬐어 조사한 grouping과 유사하여, uvsH, uvsC, uvsB와 synergistic interaction을 보였다. 하지만, quiescent conidia 상태에서의 additive effect를 보인 uvsI와 uvsF 돌연변이체는 4h germination 후에는 epistatic interaction을 나타내었다. uvsI 돌연변이체의 Intergenic-intragenic recombination frequency는 야생주와 유사하였다.

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Screening for Del 185 AG and 4627C>A BRCA1 Mutations in Breast Cancer Patients from Lahore, Pakistan

  • Aziz, Faiza;Fatima, Warda;Mahmood, Saqib;Khokher, Samina
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.1725-1727
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    • 2016
  • Breast cancer contributes to approximately 23% of the cancer cases identified and 14% of cancer related deaths worldwide. Including a strong association between genetic and environmental factors, breast cancer is a complex and multi factorial disorder. Two high penetration breast cancer susceptibility genes (BRCA1 and BRCA2) have been identified, and germ line mutations in these are thought to account for between 5% and 10% of all breast cancer cases. The human BRCA1 gene, located on 17q, is involved in the regulation of cell proliferation by aiding in DNA repair, transcriptional responses to DNA damage and cell cycle check points. Mutations in this gene enhance cell proliferation and facilitate formation of tumors. Two mutations, the 185 deletion of AG and the 4627 substitution from C to A, are founder mutations in the BRCA1 gene for breast cancer in Asian populations. Allele specific PCR was performed to detect these selected mutations in 120 samples. No mutation of 4627 C to A was detected in the samples and only one of the patients had the 185 del AG mutation in the heterozygous condition. Our collected samples had lower consanguinity and family history indicating the greater involvement of environmental as compared to genetic factors.

Alterations of Gene Expression by Beta-tricalcium Phosphate in Osteoblast-like MG63 Cells

  • Jeon, Jae-Yun;Im, Tae-Yun;Jeon, Seung-Hwan;Hwang, Kyung-Gyun;Park, Chang-Joo
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제33권4호
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    • pp.308-313
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    • 2011
  • Purpose: Beta-tricalcium phosphate (${\beta}$-TCP) is a synthetic calcium phosphate ceramic that has widely been used as a bone material to repair bone defects. Despite many clinical studies, the molecular mechanism whereby this biomaterial alters the gene expression in osteoblasts to promote bone formation is poorly understood. Thus, we attempted to address this question by using microarray techniques to identify the genes that are differentially regulated in osteoblasts exposed to ${\beta}$-TCP. Methods: By using DNA microarrays, we identified several genes whose expression levels were significantly up- or down-regulated in osteoblast-likeMG-63cells cultured with ${\beta}$-TCP at a concentration of 100 mg/10 ml for 24 hours. Results: The differentially expressed genes covered a broad range of functional activities: signal transduction, transcription, cell cycle regulation, vesicular transport, apoptosis, immunity, cytoskeletal elements and cell proliferation and differentiation. Conclusion: The gene expression changes related to cell proliferation and differentiation, vesicle transport, immunity and defense could affect the osteogenic activities of osteoblasts for bone regeneration. However, further studies will be required to verify the relative importance of these genes in bone formation, their temporal and spatial expression patterns and their interactions with each other.

Distinct mutations in MLH1 and MSH2 genes in Hereditary Non-polyposis Colorectal Cancer (HNPCC) families from China

  • Wei, Wenqian;Liu, Fangqi;Liu, Lei;Li, Zuofeng;Zhang, Xiaoyan;Jiang, Fan;Shi, Qu;Zhou, Xiaoyan;Sheng, Weiqi;Cai, Sanjun;Li, Xuan;Xu, Ye;Nan, Peng
    • BMB Reports
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    • 제44권5호
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    • pp.317-322
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    • 2011
  • Hereditary non-polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inheritance syndrome. HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions. Our study aimed to identify the patterns of hMSH2 and hMLH1 mutations in Chinese HNPCC patients. Ninety-eight unrelated families from China meeting Amsterdam or Bethesda criteria were included in our study. Germline mutations in MLH1 and MSH2 genes, located in the exons and the splice-site junctions, were screened in the 98 probands by direct sequencing. Eleven mutations were found in ten patients (11%), with six in MLH1 (54.5%) and five in MSH2 (45.5%) genes. One patient had mutations in both MLH1 and MSH2 genes. Three novel mutations in MLH1 gene (c.157_160delGAGG, c.2157dupT and c.-64G>T) were found for the first time, and one suspected hotspot in MSH2 (c.1168C>T) was revealed.

Effects of p53 Codon 72 and MDM2 SNP309 Polymorphisms on Gastric Cancer Risk among the Iranian Population

  • Moradi, Mohammad-Taher;Salehi, Zivar;Aminian, Keyvan;Yazdanbod, Abbas
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권17호
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    • pp.7413-7417
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    • 2014
  • Background: Development of gastric cancer (GC) is a multistep process that requires alterations in the expression of oncogenes and tumor suppressor genes, occurring over several decades. The p53 tumor suppressor protein is involved in cell-cycle control, apoptosis and DNA repair. One of the most important regulators of p53 is MDM2, which acts as a negative regulator in the p53 pathway. Based on the key role of p53 and MDM2 in tumor suppression, polymorphisms that cause change in their function might affect cancer risk. We therefore elevated associations of the polymorphisms of p53 (R72P) and MDM2 (SNP309) with GC in Iran. Materials and Methods: A total of 104 patients with gastric cancer and 100 controls were recruited. Genomic DNA was extracted from fresh gastric samples. Genotyping of the p53 and MDM2 genes was performed using allele specific PCR (AS-PCR). Results: There was no significant difference between the p53 codon 72 polymorphism distribution in control and patient groups (p=0.54), but the G allele of MDM2 was found to be over-represented in patients (p=0. 01, Odds Ratio=2. 08, 95% Confidence Interval= 1.37-4.34). Conclusions: The p53 R72P seems not to be a potential risk factor for development of GC among Iranian patients, but our data suggest that MDM2 SNP309 might modify the risk related to GC.

오수유 투여가 자성생쥐의 생식능력과 caspase-3, MAPK 및 MPG유전자 발현에 미치는 영향 (Effect of Evodiae Fructus on the ovarian function and gene expression of caspase-3, MAP kinase and MPG in female mice)

  • 이자영;김동철
    • 대한한방부인과학회지
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    • 제22권2호
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    • pp.60-78
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    • 2009
  • Purpose: These experiments were undertaken to evaluate the effect of administration of Evodiae Fructus on ovarian functions and differential gene expressions related caspase-3, MAPK and MPG in female mice. Methods: We administered the Evodiae Fructus to 6-week-old female ICR mice for 4, 8, or 12 days. With different concentration of Evodiae Fructus, the female mice were injected PMSG and hCG for ovarian hyperstimulation. The mice divided into 3 groups for each experiment. We chose the caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair. Results: In case of 4, 8, 12 day of Evodiae Fructus, we were examined the mean number of total ovulated oocytes and the number of morphologically normal oocytes. We were also examined the embryonic developmental competence in vitro. In addition we were also examined the differential expression of cell viability related genes, caspase-3, MAPK and MPG according to concentration and duration of Evodiae Fructus administration. MPG gene expressions for cell viability and DNA repaie were increased in dose dependent manner than that of control group in 4-day administration group. Conclusion: It is suggested that the medication of Evodiae Fructus has beneficial effect on reproductive functions of female mice via promotion of cell proliferation.

피부각질세포 HaCaT에서 진세노사이드 Rb1에 의한 유전자 발현 양상 (Gene Expression Profiling by Ginsenoside Rb1 in Keratinocyte HaCaT Cells)

  • 이동우;김정민;방인석
    • 생명과학회지
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    • 제29권5호
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    • pp.514-523
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    • 2019
  • 인삼(Panax ginseng C. A. Meyer)의 사포닌 진세노사이드 Rb1이 처리된 인간 피부각질세포 HaCaT에서 microarray 분석 및 발현이 증가된 세포사멸 반응에 대한 작용기전을 연구하였다. HaCaT 세포에 진세노사이드 Rb1의 처리로 세포사멸, 유사분열 세포주기의 G2/M 전이, 세포분열, 핵분열, 그리고 단백질 수송 등의 작용기전에 관여하는 유전자들이 2 배 이상 발현이 증가된 것으로 나타났으며, DNA 수선, 감수 핵분열, 그리고 세포외기질 체계 등의 작용기전에 관여하는 유전자들은 2 배 이상 발현이 감소된 것으로 나타났다. 특히 세포사멸 신호전달은 FAS와 PLA2G4A를 경유하는 것으로 나타났으며, 이들 유전자의 상위 조절자로 STAT3가 예측되었다. 세포사멸 반응 경유 유전자 FAS와 PLA2G4A의 활성을 qPCR로 확인한 결과, FAS 유전자는 $10{\mu}g/ml$의 진세노사이드 Rb1를 24시간 동안 처리하였을 경우 약 2 배의 발현 증가와, PLA2G4A 유전자는 6시간 처리부터 약 2 배로 증가되어 24시간 동안 처리시 2 배 이상의 유전자 발현이 증가되었다. 한편 STAT3-siRNA를 이용한 knock-down 실험에서 FAS의 발현 감소와 PLA2G4A의 발현 증가로 상위 조절자 STAT3로부터 FAS 만을 경유하는 것을 알 수 있었다. 이상의 결과 진세노사이드 Rb1의 처리에 의해 상위 조절자인 STAT3는 FAS를 경유하여 세포사멸을 유도하는 것임을 알 수 있다.

Endoplasmic recticulum stress와 관련된 유전자기능과 전사조절인자의 In silico 분석 (In Silico Analysis of Gene Function and Transcriptional Regulators Associated with Endoplasmic Recticulum (ER) Stress)

  • 김태민;여지영;박찬선;이문수;정명호
    • 생명과학회지
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    • 제19권8호
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    • pp.1159-1163
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    • 2009
  • ER stress에 관련된 유전자의 기능변화와 전사조절인자 분석하기 위해 ER stress를 유도한 간세포에서 expression microarray로 유전자 발현을 확보한 후 GSECA로 분석하였다. ER stress가 유도되면, ER에 주어지는 과도한 부하를 감소시키는 기능들이 증가하는 반면, ER stress가 더 증가함에 따라 ATP 생성이나 DNA repair, 더 나아가 세포분열의 기능이 감소하는 등 세포가 damage을 받음을 알 수 있었다. ER stress에 관련된 전사조절인자로는 FOX04, AP-1, FOX03, HNF4, IRF-1, GATA 등의 전사조절인자들이 ER stress에 의해 발현이 증가하는 유전자들의 promoter에 공통적으로 존재하였으며, E2F, Nrf-1, Elk-1, YY1, CREB, MTF-1, STAT-1, ATF 등의 전사인자들이 발현이 감소하는 유전자들의 promoter에서 공통적으로 존재하여, 이들의 전사인자들이 ER stress에 의한 유전자의 발현조절에 중요한 역할을 하는 전사조절인자임을 알 수 있었다.