• Title/Summary/Keyword: DNA Repair

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Polo-like kinase-1 in DNA damage response

  • Hyun, Sun-Yi;Hwan, Hyo-In;Jang, Young-Joo
    • BMB Reports
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    • v.47 no.5
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    • pp.249-255
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    • 2014
  • Polo-like kinase-1 (Plk1) belongs to a family of serine-threonine kinases and plays a critical role in mitotic progression. Plk1 involves in the initiation of mitosis, centrosome maturation, bipolar spindle formation, and cytokinesis, well-reported as traditional functions of Plk1. In this review, we discuss the role of Plk1 during DNA damage response beyond the functions in mitotsis. When DNA is damaged in cells under various stress conditions, the checkpoint mechanism is activated to allow cells to have enough time for repair. When damage is repaired, cells progress continuously their division, which is called checkpoint recovery. If damage is too severe to repair, cells undergo apoptotic pathway. If damage is not completely repaired, cells undergo a process called checkpoint adaptation, and resume cell division cycle with damaged DNA. Plk1 targets and regulates many key factors in the process of damage response, and we deal with these subjects in this review.

Molecular Links between Alcohol and Tobacco Induced DNA Damage, Gene Polymorphisms and Patho-physiological Consequences: A Systematic Review of Hepatic Carcinogenesis

  • Mansoori, Abdul Anvesh;Jain, Subodh Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4803-4812
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    • 2015
  • Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

Molecular Cloning and Characterization of a recA-like Gene Induced by DNA Damage from a Fluorescent Pseudomonas sp.

  • Ok Bong Kim;Na Young Kim;Jae Hoon Jeong;Si Wouk Kim;Hye Gwang Jeong;Seong Myeong Yoon;Jong Kun Park;Jung Sup Lee
    • Animal cells and systems
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    • v.3 no.2
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    • pp.229-236
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    • 1999
  • The recA gene plays a central role in genetic recombination and SOS DNA repair in Escherichia coli (E. coli). We have previously identified a 42 kDa RecA-like protein inducible by a variety of DNA damages from a fluorescent Pseudomonas strain sp. and characterized its inducible kinetics. In the present study, we cloned and characterized the gene encoding the RecA-like protein by immunological screening of Pseudomonas genomic expression library using polyclonal E. coli anti-RecA antibodies as a probe. From 10$^{5}$ plaques screened, five putative clones were finally isolated. Southern blot analysis indicated that four clones had the same DNA inserts and the recA-like gene was located within the 3.2 kb EcoRI fragment of Pseudomonas chromosomal DNA. In addition, the cloned recA-like gene was transcribed into an RNA transcript approximately 1.1 kb in size, as judged by Northern blot analysis. The cellular level of RNA transcript of the cloned recA-like gene was increased to an average of 5.15- fold upon treatment with DNA damaging agents such as ultraviolet (UV)- light, nalidixic acid (NA), methyl methanesulfonate (MMS), and mitomycin-C (MMC). These results suggest that the cloned gene is inducible by DNA damage similarly to the recA gene in E. coli. However, the cloned gene did not restore the DNA damage sensitivity of the E. coli recA-mutant.

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NMR PEAK ASSIGNMENT FOR THE ELUCIDATION OF THE SOLUTION STRUCTURE OF T4 ENDONUCLEASE V

  • Im, Hoo-Kang;Jee, Jun-Goo;Yu, Jun-Suk;Lee, Bong-Jin
    • Proceedings of the Korean Biophysical Society Conference
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    • 1996.07a
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    • pp.18-18
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    • 1996
  • Bacteriophage T4 endonuclease V initiates the repair of ultraviolet (UV)-induced pyrimidine dimer photoproducts in duplex DNA. The mechanism of DNA strand cleavage involves four sequential steps: linear diffusion along dsDNA, pyrimidine dimer-specific binding, pyrimidine dimer-DNA glycosylase activity, and AP lyase activity. (omitted)

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A Study of Error Detection and Repair on DNA Duplicate Structure (DNA 이중나선구조에서의 오류 검출 및 복구방법연구)

  • Kim, Soke-Hwan;Hur, Chang-Wu
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2011.10a
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    • pp.327-330
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    • 2011
  • 살아있는 생명체는 세포로 구성되며 성장 분열을 통해 스스로 복제할 수 있는 능력을 지녔다. DNA 상의 변이, 즉 돌연변이는 자손의 생존과 번식에 불리하게 작용할 수 있고 이점을 줄 수 있는 양면성을 지녔다. 본 연구에서는 DNA 이중나선은 복제 주형으로 사용되기 위해서는 먼저 이중나선이 열리고 단일 가닥으로 분리되어야 한다. 이중 나선구조결합에서의 결합의 오류부분의 위치를 찾아내고 복구하는 방법을 제시한다.

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Association of Two Polymorphisms of DNA Polymerase Beta in Exon-9 and Exon-11 with Ovarian Carcinoma in India

  • Khanra, Kalyani;Panda, Kakali;Bhattacharya, Chandan;Mitra, A.K.;Sarkar, Ranu;Bhattacharyya, Nandan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1321-1324
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    • 2012
  • Background: DNA polymerase beta ($pol{\beta}$) is a key enzyme in the base excision repair pathway. It is 39kDa protein, with two subunits, one large subunit of 31 kDa having catalytic activity between exon V to exon XIV, and an 8 kDa smaller subunit having single strand DNA binding activity. Exons V to VII have double strand DNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XII to XIV the dNTP selection activity. Aim: To examine the association between $pol{\beta}$ polymorphisms and the risk of ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastatic normal samples from the same patients. In this study, mutational analysis of $pol{\beta}$ genomic DNA was undertaken using primers from exons IX to XIV - the portion having catalytic activity. Results: We detected alteration in DNA polymerase beta by SSCP. Two specific heterozygous point mutations of $pol{\beta}$ were identified in Exon 9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlation study involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous type with a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type and stage IV together have shown Pearson ${\chi}^2$ value of 3.28 with likelihood ratio of 4.4 (p=0.07) with OR =2.08 (0.3-14.55). This indicates that there is a tendency of correlation among polymorphism 2, serous type and stage IV, indicating a risk factor for ovarian cancer. Conclusion: Hence, the results indicate that there is a tendency for $pol{\beta}$ polymorphisms being a risk factor for ovarian carcinogenesis in India.

DNA Repair Characteristics of MRC-5 and SK-N-SH Irradiated with Proton Beam (양성자빔 조사에 따른 MRC-5와 SK-N-SH의 DNA 손상 후 회복 특성)

  • Choi, Eun-Ae;Lee, Bong-Soo;Cho, Young-Ho
    • Journal of radiological science and technology
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    • v.34 no.4
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    • pp.333-339
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    • 2011
  • The purpose of this study is to compare DNA repair characteristics of normal fibroblast cell (MRC-5) and neuroblastoma cell (SK-N-SH) induced by proton beam. Cells were irradiated with 2Gy, 5Gy and 8Gy proton beam. The rate of DNA rejoining was measured by alkaline version of the comet assay. After a repair time, tail moment was measured again. The tail moment of MRC-5 was lower than SK-N-SH. However, after 8Gy of exposure, the tail moment of MRC-5 was measured as 50.320223.17155 which represents dangerous level of DNA damage. The cells were repaired practically within 25 hours after 2 and 5Gy of exposure while they were not fully recovered after 8Gy of exposure. Especially, tail moment of MRC-5 after 25 hours was 18.15364.42849. In the distal declining edge of SOBP, the RBE value is increased by high LET. The RBE differences of SOBP in high-dose were greater than low-dose. After the high-dose exposure, MRC-5 of normal fibroblast cell could lead to lasting DNA damage as shown in this study. In conclusion, we has to pay special attention when the region of the treatment volume is close to sensitive tissues.

Drosophila melanogaster: a Model for the Study of DNA Damage Checkpoint Response

  • Song, Young-Han
    • Molecules and Cells
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    • v.19 no.2
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    • pp.167-179
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    • 2005
  • The cells of metazoans respond to DNA damage by either arresting their cell cycle in order to repair the DNA, or by undergoing apoptosis. This response is highly conserved across species, and many of the genes involved in this DNA damage response have been shown to be inactivated in human cancers. This suggests the importance of DNA damage response with regard to the prevention of cancer. The DNA damage checkpoint responses vary greatly depending on the developmental context, cell type, gene expression profile, and the degree and nature of the DNA lesions. More valuable information can be obtained from studies utilizing whole organisms in which the molecular basis of development has been well established, such as Drosophila. Since the discovery of the Drosophila p53 orthologue, various aspects of DNA damage responses have been studied in Drosophila. In this review, I will summarize the current knowledge on the DNA damage checkpoint response in Drosophila. With the ease of genetic, cellular, and cytological approaches, Drosophila will become an increasingly valuable model organism for the study of mechanisms inherent to cancer formation associated with defects in the DNA damage pathway.

NMR Study of Temperature-Dependent Single-Stranded DNA Binding Affinity of Human Replication Protein A

  • Kim, Min-Gyu;Shin, Tae-Hoan;Choi, Seo-Ree;Choi, Jae-Gyu;Lee, Joon-Hwa
    • Journal of the Korean Magnetic Resonance Society
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    • v.20 no.3
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    • pp.66-70
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    • 2016
  • The replication protein A (RPA), is a heterotrimer with 70, 32 and 14 kDa subunits and plays a crucial role in DNA replication, recombination, and repair. The largest subunit, RPA70, binds to single-stranded DNA (ssDNA) and mediates interactions with many cellular and viral proteins. In this study, we performed nuclear magnetic resonance experiments on the complex of the DNA binding domain A of human RPA70 (RPA70A) with ssDNA, d(CCCCC), at various temperatures, to understand the temperature dependency of ssDNA binding affinity of RPA70A. Essential residues for ssDNA binding were conserved while less essential parts were changed with the temperature. Our results provide valuable insights into the molecular mechanism of the ssDNA binding of human RPA.