UV-B辐射和NaCl胁迫对绿豆幼苗叶片DNA损伤的复合效应

研究了0·4W/m2UV-B辐射和0·4%NaCl胁迫对两绿豆品种中绿_1和秦豆-20(PhaseolusraditusL.cv.Zhongl櫣-1andQindou-20)幼苗叶片DNA损伤的复合效应。结果表明:(1)中绿-1抗UV-B辐射和NaCl胁迫的能力均强于秦豆-20;NaCl胁迫能降低中绿-1UV-B敏感性,但对秦豆-20UV-B敏感性无明显影响。(2)两逆境因子单独胁迫或复合胁迫下DNA增色效应均明显降低,但中绿-1降低程度小于秦豆-20,复合胁迫下降低程度小于单独NaCl胁迫下。(3)UV-B辐射诱导的中绿-1DNA链内环丁烷嘧啶二聚体(CPD)累积量明显低于秦豆-20;NaCl胁迫能降低UV-B诱导的中绿-1CPD累积,而对UV-B诱导的秦豆-20CPD累积无影响。(4)各种胁迫处理均导致两品种幼苗DNA含量降低,但两品种间相比中绿-1降低程度较大。结果说明UV-B辐射不仅能诱导DNA链内交联形成CPD,而且能诱导DNA链间交联和DNA含量降低,且不同绿豆品种或同一品种在有无NaCl胁迫时UV-B敏感性的差异主要与CPD累积量和DNA链间交联程度有关。     

Dihydropyrimidine Dehydrogenase Deficiency Caused by a Novel Genomic Deletion c.505_513del of DPYD

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of the pyrimidine degradation pathway. In a patient presenting with convulsions, psychomotor retardation and Reye like syndrome, strongly elevated levels of uracil and thymine were detected in urine. No DPD activity could be detected in peripheral blood mononuclear cells. Analysis of the gene encoding DPD (DPYD) showed that the patient was homozygous for a novel c.505_513del (p.169_171del) mutation in exon 6 of DPYD.     

嘧啶核苷的研究进展

嘧啶核苷包括尿嘧啶核苷和胞嘧啶核苷,其在食品工业和医药行业上应用广泛。介绍了嘧啶核苷的用途、测定方法、生产方法等;根据代谢控制发酵原理,以尿苷生产菌的选育为例,详细介绍了嘧啶核苷生产菌的育种策略,并对嘧啶核苷生产菌的育种实例、育种展望进行了综述。     

Rates of heat-induced pyrimidine alterations in synthetic polydeoxyribonucleotides

Hydrolytic damages to DNA can occur at physiological conditions. The possible role of DNA conformation on the distribution of such alterations of pyrimidines was investigated. Model compounds used were the synthetic alternating copolymer poly(dG-dC):poly(dG-dC) and the homopolymer poly(dG):poly(dC). Base damages were assayed by paper chromatography using polymers radioactively labeled in cytosine. Conformational changes were assayed by circular dichroic spectral changes. Incubation and heating of the polymers in 1 mM MnCl₂ caused the spectral shift reported for the left-handed Z-DNA conformation in the alternating copolymer and the change reported for the triple helix in the homopolymer. After incubation in 85°C, incidences of base damages were compared between the polymers. The presence of manganese reduced depyrimidination in both polymers. Rates of cytosine deamination to uracil were substantial and did not vary among the various conformational states.     

XIAP is essential for shear stress-enhanced Tyr-576 phosphorylation of FAK

In endothelial cells, X-chromosome linked inhibitor of apoptosis protein (XIAP) regulates cell survival, migration and adhesion. We have recently found that XIAP recruits focal adhesion kinase (FAK) into integrin-associated focal adhesions, controlling cell migration. However, little is understood about the molecular mechanisms by which FAK modulation is controlled by XIAP. In this study, we show that XIAP modulates FAK activity through the control of FAK phosphorylation. In bovine aortic endothelial cells (BAEC), phosphorylation of Tyr-576 in FAK is elevated by laminar shear stress. This elevated phosphorylation appears to be responsible for shear stress-stimulated ERK activation. We found that XIAP knockdown reduces shear stress-enhanced phosphorylation of Tyr-576 and induces shear stress-triggered translocation of FAK into nucleus. Nuclear translocation of FAK reduces contact between FAK and Src, a kinase which phosphorylates Tyr-576. This spatial segregation of FAK from Src decreases Tyr-576 phosphorylation and thus shear-stimulated ERK activation. Taken together, our results demonstrate that XIAP plays a key role in shear stress-stimulated ERK activation by maintaining the Src-accessible location of FAK.     

1,2,3‐Triazole Tagged 3H‐Pyrano[2,3‐d]pyrimidine‐6‐carboxylate Derivatives: Synthesis,in Vitro Cytotoxicity,Molecular Docking and DNA Interaction Studies

A series of novel ethyl 2,7‐dimethyl‐4‐oxo‐3‐[(1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]‐4,5‐dihydro‐3H‐pyrano[2,3‐d]pyrimidine‐6‐carboxylate derivatives 7a – 7m were efficiently synthesized employing click chemistry approach and evaluated for in vitro cytotoxic activity against four tumor cell lines: A549 (human lung adenocarcinoma cell line), HepG2 (human hematoma), MCF‐7 (human breast adenocarcinoma), and SKOV3 (human ovarian carcinoma cell line). Among the compounds tested, the compounds 7a , 7b , 7f , 7l , and 7m have shown potential and selective activity against human lung adenocarcinoma cell line (A549) with IC₅₀ ranging from 0.69 to 6.74 μm . Molecular docking studies revealed that the compounds 7a , 7b , 7f , 7l , and 7m are potent inhibitors of human DNA topoisomerase‐II and also showed compliance with stranded parameters of drug likeness. The calculated binding constants, k_b, from UV/VIS absorptional binding studies of 7a and 7l with CT‐DNA were 10.77 × 10⁴, 6.48 × 10⁴, respectively. Viscosity measurements revealed that the binding could be surface binding mainly due to groove binding. DNA cleavage study showed that 7a and 7l have the potential to cleave pBR322 plasmid DNA without any external agents.