脱プリン脱ピリミジン部位エンドヌクレアーゼ
- 関
- AP endonuclease
WordNet
- a nuclease that cleaves nucleic acids at interior bonds and so produces fragments of various sizes
UpToDate Contents
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English Journal
- Base Excision Repair of Tandem Modifications in a Methylated CpG Dinucleotide.
- Sassa A1, Ağlayan M, Dyrkheeva NS, Beard WA, Wilson SH.Author information 1NIEHS, National Institutes of Health, United States.AbstractCytosine methylation and demethylation in tracks of CpG dinucleotides is an epigenetic mechanism for control of gene expression. The initial step in the demethylation process can be deamination of 5-methylcytosine producing the TpG alteration and T:G mispair, and this step is followed by thymine DNA glycosylase (TDG) initiated base excision repair (BER). A further consideration is that guanine in the CpG dinucleotide may become oxidized to 7,8-dihydro-8-oxoguanine (8-oxoG), and this could affect the demethylation process involving TDG-initiated BER. However, little is known about the enzymology of BER of tandemly altered CpG dinucleotides; e.g., Tp8-oxoG. Here, we investigated interactions between this altered dinucleotide and purified BER enzymes, the DNA glycosylases TDG and 8-oxoG DNA glycosylase 1 (OGG1), apurinic/apyrimidinic (AP) endonuclease 1, DNA polymerase β and DNA ligases. The overall TDG-initiated BER of the Tp8-oxoG dinucleotide is significantly reduced. Specifically, TDG and DNA ligase activities are reduced by a 3[prime]-flanking 8-oxoG. In contrast, OGG1-initiated BER pathway is blocked due to the 5[prime]-flanking T:G mispair; this reduces OGG1, AP endonuclease 1, and DNA polymerase β activities. Further, in TDG-initiated BER, TDG remains bound to its product AP site blocking OGG1 access to the adjacent 8-oxoG. These results reveal BER enzyme specificities enabling suppression of OGG1-initiated BER and coordination of TDG-initiated BER at this tandem alteration in the CpG dinucleotide.
- The Journal of biological chemistry.J Biol Chem.2014 Apr 2. [Epub ahead of print]
- Cytosine methylation and demethylation in tracks of CpG dinucleotides is an epigenetic mechanism for control of gene expression. The initial step in the demethylation process can be deamination of 5-methylcytosine producing the TpG alteration and T:G mispair, and this step is followed by thymine DNA
- PMID 24695738
- APE1 incision activity at abasic sites in tandem repeat sequences.
- Li M1, Völker J2, Breslauer KJ3, Wilson DM 3rd4.Author information 1Laboratory of Molecular Gerontology, National Institutes of Health, National Institute on Aging, Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224.2Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854.3Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854; Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901.4Laboratory of Molecular Gerontology, National Institutes of Health, National Institute on Aging, Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224. Electronic address: wilsonda@mail.nih.gov.AbstractRepetitive DNA sequences, such as are present in micro- and mini-satellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modifications, strand breaks and abasic sites, have a propensity to adopt non-canonical DNA forms modulated by the position(s) of the lesion(s), and, when not properly processed, can contribute to genome instability that underlies aging and disease development. Knowledge of the repair efficiencies of DNA damage within such repetitive sequences is therefore crucial for understanding the impact of such domains on genomic integrity. In the present study, using strategically designed oligonucleotide substrates, we determined the ability of human apurinic/apyrimidinic endonuclease 1 (APE1) to cleave at AP sites in a collection of tandem DNA repeat landscapes involving telomeric and CAG/CTG repeat sequences. Our studies reveal the differential influence of domain sequence, conformation, and AP site location/relative positioning on the efficiency of APE1 binding and strand incision. Intriguingly, our data demonstrate that APE1 endonuclease efficiency correlates with the thermodynamic stability of the DNA substrate. We discuss how these results have both predictive and mechanistic consequences for understanding the success and failure of repair protein activity associated with such oxidatively sensitive, conformationally plastic/dynamic repetitive DNA domains.
- Journal of molecular biology.J Mol Biol.2014 Apr 1. pii: S0022-2836(14)00159-4. doi: 10.1016/j.jmb.2014.03.014. [Epub ahead of print]
- Repetitive DNA sequences, such as are present in micro- and mini-satellites, telomeres, and trinucleotide repeats (linked to fragile X syndrome, Huntington disease, etc.), account for nearly 30% of the human genome. These domains exhibit enhanced susceptibility to oxidative attack to yield base modi
- PMID 24703901
- Genistein Alleviates Radiation-Induced Pneumonitis by Depressing Ape1/Ref-1 Expression to Down-regulate Inflammatory Cytokines.
- Liu GD1, Xia L, Zhu JW, Ou S, Li MX, He Y, Luo W, Li J, Zhou Q, Yang XQ, Shan JL, Wang G, Wang D, Yang ZZ.Author information 1Eighth Department, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, 400042, People's Republic of China.AbstractThe aim of the study was to investigate the role of genistein in alleviating radiation-induced pneumonitis (RIP) through down-regulating levels of the inflammatory cytokines by inhibiting the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1). Fifty female C57BL/6J mice (8 weeks old) were randomly divided into a control group, a pure irradiation (IR) group and a genistein + IR group. At the four time points after IR, hematoxylin, and Masson's trichrome stainings were used to examine the pathological changes and collagen fiber deposition. Flow cytometry was used to detect reactive oxygen system (ROS) changes, EMSA was used to estimate the nuclear factor kappa B (NF-κB) transcriptional activities and an ELISA assay was used to measure the levels of TGF-β1, IL-1β, TNF-α, and IL-6 in the serum and bronchoalveolar lavage fluid (BALF) 2 weeks after IR. The pathological detection results showed acute inflammatory/fibrinoid exudation of the thoracic tissue after IR, which was significantly alleviated with genistein. The IR-induced an APE1 protein expression increase and NF-κB was effectively suppressed by genistein (P < 0.05). The induction of the inflammatory cytokines TGF-β1, IL-1β, TNF-α, and IL-6 by IR were in turn inhibited in the serum and BALF of the genistein-pretreated mice (P < 0.05). In addition, the ROS production was significantly boosted in the A549 cells after IR, which could be down-regulated by the pretreatment of genistein. The results demonstrate that genistein alleviates RIP by attenuating the inflammatory response in the initiation of RIP. A possible target of genistein is the Ape1/ref-1, which regulates key inflammatory cytokines by activating the NF-κB.
- Cell biochemistry and biophysics.Cell Biochem Biophys.2014 Mar 23. [Epub ahead of print]
- The aim of the study was to investigate the role of genistein in alleviating radiation-induced pneumonitis (RIP) through down-regulating levels of the inflammatory cytokines by inhibiting the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1). Fifty female C57BL/6J mice (
- PMID 24659138
Japanese Journal
- Formation of the Nitrative DNA Lesion 8-Nitroguanine is Associated with Asbestos Contents in Human Lung Tissues: A Pilot Study
- Apurinic/apyrimidinic endonuclease-1 (APE-1) is overexpressed via the activation of NF-κB-p65 in MCP-1-positive esophageal squamous cell carcinoma tissue
- Journal of Clinical Biochemistry and Nutrition 52(2), 112-119, 2013
- NAID 130004466710
- Knock down of the dual functional protein apurinic/apyrimidinic endonuclease 1 enhances the killing effect of hematoporphrphyrin derivative-mediated photodynamic therapy on non-small cell lung cancer cells in vitro and in a xenograft model
Related Links
- 1. Antioxid Redox Signal. 2014 Feb 1;20(4):678-707. doi: 10.1089/ars.2013.5492. Epub 2013 Aug 20. Human apurinic/apyrimidinic endonuclease 1. Li M(1), Wilson DM 3rd. Author information: (1)Intramural ...
- 1. J Biol Chem. 2015 Jan 30;290(5):3057-68. doi: 10.1074/jbc.M114.621995. Epub 2014 Dec 9. Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) redox function negatively regulates NRF2. Fishel ML(1), Wu ...
★リンクテーブル★
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- 関
- AP lyase、apurinic endonuclease、apurinic-apyrimidinic endonuclease
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- 英
- apurinic-apyrimidinic endonuclease、AP endonuclease
- 関
- 脱プリン部位エンドヌクレアーゼ、APエンドヌクレアーゼ、APリアーゼ
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エンドヌクレアーゼ、・リヌクレオチド内部加水分解酵素
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ピリミジン塩基のない、脱ピリミジン塩基の
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プリン塩基のない、脱プリン塩基の
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