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971.
972.
Umakanta Swain Gilgi Friedlander Urmila Sehrawat Avital Sarusi-Portuguez Ron Rotkopf Charlotte Ebert Tamar Paz-Elizur Rivka Dikstein Thomas Carell Nicholas E. Geacintov Zvi Livneh 《International journal of molecular sciences》2021,22(13)
TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here, we show that TENT4A regulates multiple biological pathways and focuses on its multilayer regulation of translesion DNA synthesis (TLS), in which error-prone DNA polymerases bypass unrepaired DNA lesions. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase η and RAD18 E3 ligase, which guides the polymerase to replication stalling sites and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD and via the long non-coding antisense RNA PAXIP1-AS2, which had no known function. Knocking down the expression of TENT4A or CYLD, or overexpression of PAXIP1-AS2 led each to reduced amounts of the RAD18 protein and DNA polymerase η, leading to reduced TLS, highlighting PAXIP1-AS2 as a new TLS regulator. Bioinformatics analysis revealed that TLS error-prone DNA polymerase genes and their TENT4A-related regulators are frequently mutated in endometrial cancer genomes, suggesting that TLS is dysregulated in this cancer. 相似文献
973.
Yoshinori Okamoto Hideto Jinno Shinji Itoh Shinya Shibutani 《International journal of molecular sciences》2021,22(13)
Human estrogens prescribed for hormone replacement therapy (HRT) are known to be potent carcinogens. To find safer estrogens, several chlorinated estrogens were synthesized and their carcinogenic potential were determined. A pellet containing either 2-chloro-17β-estradiol (2-ClE2) or 4-chloro-17β-estradiol (4-ClE2) was implanted subcutaneously for 52 weeks into August Copenhagen Irish (ACI) rats, a preferred animal model for human breast cancer. 17β-Estradiol (E2) frequently induced mammary tumors while both 2-ClE2 and 4-ClE2 did not. Their 17α-ethinyl forms, thought to be orally active estrogens, were also synthesized. Neither 2-chloro-17α-ethinylestradiol (2-ClEE2) nor 4-chloro-17α-ethinylestradiol (4-ClEE2) induced tumors. The less carcinogenic effects were supported by histological examination of mammary glands of ACI rats treated with the chlorinated estrogens. A chlorine atom positioned at the 2- or 4-position of E2 may prevent the metabolic activation, resulting in reducing the carcinogenicity. 2-ClE2 and 4-ClE2 administered subcutaneously and 2-ClEE2 and 4-ClEE2 given orally to ovariectomized rats all showed uterotrophic potency, albeit slightly weaker than that of E2. Our results indicate that less carcinogenic chlorinated estrogens retaining estrogenic potential could be safer alternatives to the carcinogenic estrogens now in use for HRT. 相似文献
974.
Janusz Blasiak Joanna Szczepanska Michal Fila Elzbieta Pawlowska Kai Kaarniranta 《International journal of molecular sciences》2021,22(13)
Age-related macular degeneration (AMD), the main cause of vision loss in the elderly, is associated with oxidation in the retina cells promoting telomere attrition. Activation of telomerase was reported to improve macular functions in AMD patients. The catalytic subunit of human telomerase (hTERT) may directly interact with proteins important for senescence, DNA damage response, and autophagy, which are impaired in AMD. hTERT interaction with mTORC1 (mTOR (mechanistic target of rapamycin) complex 1) and PINK1 (PTEN-induced kinase 1) activates macroautophagy and mitophagy, respectively, and removes cellular debris accumulated over AMD progression. Ectopic expression of telomerase in retinal pigment epithelium (RPE) cells lengthened telomeres, reduced senescence, and extended their lifespan. These effects provide evidence for the potential of telomerase in AMD therapy. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may be involved in AMD pathogenesis through decreasing oxidative stress and senescence, regulation of vascular endothelial growth factor (VEGF), and improving autophagy. PGC-1α and TERT form an inhibitory positive feedback loop. In conclusion, telomerase activation and its ectopic expression in RPE cells, as well as controlled clinical trials on the effects of telomerase activation in AMD patients, are justified and should be assisted by PGC-1α modulators to increase the therapeutic potential of telomerase in AMD. 相似文献
975.
976.
Niu L Mantri N Li CG Xue C Wohlmuth H Pang EC 《Journal of the science of food and agriculture》2011,91(7):1310-1315
BACKGROUND: Food adulteration remains a major global concern. DNA fingerprinting has several advantages over chemical and morphological identification techniques. DNA microarray‐based fingerprinting techniques have not been used previously to detect adulteration involving dried commercial samples of closely related species. Here we report amplification of low‐level DNA obtained from dried commercial ginseng samples using the Qiagen? REPLI‐g® Kit. Further, we used a subtracted diversity array (SDA) to fingerprint the two ginseng species, Panax ginseng and Panax quinquefolius, that are frequently mixed for adulteration. RESULTS: The two ginseng species were successfully discriminated using SDA. Further, SDA was sensitive enough to detect a deliberate adulteration of 10% P. quinquefolius in P. ginseng. Thirty‐nine species‐specific features including 30 P. ginseng‐specific and nine P. quinquefolius‐specific were obtained. This resulted in a feature polymorphism rate of 10.5% from the 376 features used for fingerprinting the two ginseng species. The functional characterization of 14 Panax species‐specific features by sequencing revealed one putative ATP synthase, six putative uncharacterized proteins, and two retroelements to be different in these two species. CONCLUSION: SDA can be employed to detect adulterations in a broad range of plant samples. Copyright © 2011 Society of Chemical Industry 相似文献
977.
研究了外源质粒DNA经胃肠道吸收可能对肝脏产生的作用机制。给Balb/c小鼠灌胃质粒pcDNA3 200μg,在灌胃后4h分离肝脏,提取肝脏的总RNA。利用寡核苷酸芯片对灌胃质粒pcDNA3后的Balb/c小鼠肝脏进行基因表达谱研究。结果发现17664个基因中,表达上调100条,表达下调41条。按基因功能分类,表达上调的基因可分为免疫应答基因、转录因子基因、信号转导基因、转运相关基因及代谢相关基因等;表达下调的基因主要为脂质代谢基因。灌胃外源质粒DNA后,肝脏组织主要表现为急性时相反应的加强、免疫反应的活化、细胞信号通路的活化以及脂质代谢途径的抑制。表明外源质粒DNA通过胃肠道途径可广泛调控肝脏的基因表达。 相似文献
978.
Walter E. Hill Dr. Kaye Wachsmuth 《Critical reviews in food science and nutrition》1996,36(1-2):123-173
Faster methods for the detection of foodborne microbial pathogens are needed. The polymerase chain reaction (PCR) can amplify specific segments of DNA and is used to detect and identify bacterial genes responsible for causing diseases in humans. The major features and requirements for the PCR are described along with a number of important variations. A considerable number of PCR‐based assays have been developed, but they have been applied most often to clinical and environmental samples and more rarely for the detection of foodborne microorganisms. Much of the difficulty in implementing PCR for the analysis of food samples lies in the problems encountered during the preparation of template DNAs from food matrices; a variety of approaches and considerations are examined. PCR methods developed for the detection and identification of particular bacteria, viruses, and parasites found in foods are described and discussed, and the major features of these reactions are summarized. 相似文献
979.
Agnieszka Koszucka Adriana Nowak 《Critical reviews in food science and nutrition》2019,59(22):3579-3596
AbstractHeterocyclic aromatic amines, acrylamide, 5-hydroxymethylfurfural, furan, polycyclic aromatic hydrocarbons, nitrosamines, acrolein, chloropropanols and chloroesters are generated toxicants formed in some foodstuffs, mainly starchy and protein-rich food during thermal treatment such as frying, roasting and baking. The formation of these chemical compounds is associated with development of aromas, colors and flavors. One of the challenges facing the food industry today is to minimize these toxicants without adversely affecting the positive attributes of thermal processing. To achieve this objective, it is essential to have a detailed understanding of the mechanism of formation of these toxicants in processed foods. All reviewed toxicants in that paper are classified as probable, possible or potential human carcinogens and have been proven to be carcinogenic in animal studies. The purpose of that review is to summarize some of the most frequent occurring heat-generated food toxicants during conventional heating, their metabolism and carcinogenicity. Moreover, conventional and microwave heating were also compared as two different heat treatment methods, especially how they change food chemical composition and which thermal food toxicants are formed during specific method. 相似文献
980.
动物明胶中3种DNA提取方法的比较研究 总被引:3,自引:0,他引:3
基于DNA水平的分子生物学检测方法,因其高特异性、高灵敏度且简便快速等优点,成为明胶动物来源鉴别检测的有效方法。但明胶的特殊加工工艺给DNA的提取带来了一定的困难。研究中选取了牛皮明胶、牛骨明胶和猪皮明胶等不同动物品种和不同动物组织来源的明胶产品,采用了试剂盒法、蛋白沉淀法和裂解抽提法等3种DNA提取方法,从DNA提取质量、提取效率及明胶动物种类来源PCR扩增等方面对3种方法进行了比较。研究结果表明,裂解抽提法所提取的明胶中的DNA质量优于前2种方法,且适合于进一步的PCR扩增检测,是适合于明胶DNA提取的有效方法。 相似文献