• YAKHAK HOEJI
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• v.37 no.6
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• pp.591-597
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• 1993

Two new 6-azauracil dioxolane nucleosides which are related to Dioxolane T and expected to have anti-HIV activity were asymmetrically synthesized. The key intermediate 8 have been synthesized in ten steps from D-mannose and condensed with 6-azauracil to give 13 and 14 after desilylation, respectively.

• KSBB Journal
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• v.9 no.4
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• pp.372-377
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• 1994

To improve L-lysine yield, pyrimidine base analogue(6-azauracil)-resistant mutants were isolated from Corynebacterium glutamicum KFCC10672 Among them the best producer, C. glutamicum CH0516, was selected and tested for L-lysine production in a $7\ell$ fermentor. It was found that the product yield obtained with C. glutamicum CH0516 was higher than that of the parent strain by 3%. In order to elucidate the gain in productivity with the 6-azauracil-resistant mutant enzymatic kinetic parameters such as aspartokinase(AKase) and aspartate carbamoyltransferase (ATCase) were measured. The Km values of AKase with C. glutamicum KFCC10672 and CH0516 were 200.0 mM and 166.7 mM and those of ATCase were 0.13 mM and 0.27 mM, respectively. However, the specific enzyme activities of AKase of C. glutamlcum KFCC10672 and CH0516 were $3.89{\times}10^{-1}$ units/mg and $4.78{\times}10^{-1}$ units/mg, and those of ATCarse were 2.20 units/mg and 1.84 units/mg, respectively. It appears that some increase in product yield with C. gluramicum CH0516 is likely due to the increased Akase activity and decreased ATCase activity.

• YAKHAK HOEJI
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• v.40 no.1
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• pp.46-51
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• 1996

Eight new D-1.3-dioxolanyl and L-1,3-oxathiolanyl nucleosides containing 5-phenyl- selenyl pyrimidine bases which are expected to have antiviral activity were synthesized. Condensation of D-1,3-dioxolane acetate and L-1,3-oxathiolane acetate with 5-phenylselenyl pyrimidines gave anomeric mixtures of their nucleosides which were separated by silicagel column chromatography.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2005.04a
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• pp.5-14
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• 2005

Recently, data from several groups have raised the concept of 'checkpoint' in transcription. As capping of nascent RNA transcript is tightly coupled to RNA polymerase II transcription, we seek to obtain direct evidence that transcripiton checkpoint via capping enzyme functions in this early regulatory step. One of temperature sensitive (ts) alleles of ceg1, a guanylyltransferase subunit of the Saccharomyces cerevisiaecapping enzyme, showed 6-azauracil (6AU) sensitivity at the permissive growth temperature, which is a phenotype that is correlated with a transcription elongational defect. This ts allele, ceg1-63 also has an impaired ability to induce PUR5 in response to a 6AU treatment. However, this cellular and molecular defect is not due to the preferential degradation of the transcript attributed from a lack of guanylyltransferase activity. On the contrary, the data suggests that the guanylyltransferase subunit of the capping enzyme plays a role in transcription elongation. First, in addition to the 6AU sensitivity, ceg1-63is synthetically lethal with elongation defective mutations of the largest subunit of RNA polymerase II. Secondly, it exhibited a lower GAL1 mRNA turn-over after glucoseshut off. Third, it decreased the transcription read through a tandem array of promoter proximal pause sites in an orientation dependent manner. Interestingly, this mutant also showed lower pass through a pause site located further downstream of the promoter. Taken together, these results suggest that the capping enzyme plays the role of an early transcription checkpoint possibly in the step of the reversion of repression by stimulating polymerase to escape from the promoter proximal arrest once RNA becomes appropriately capped.

• YAKHAK HOEJI
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• v.38 no.6
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• pp.775-781
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• 1994

$({\pm})-Dioxolane-T$ and$({\pm})-BCH-189$ are know to possess anti-HIV activities, and less to xicities compared to other dideoxynucleoside AIDS drugs. We have synthesized 34 different enantiomerically pure nucleosides by glycosylation of L-1,3-dioxolanyl acetate and L-1,3-oxathiolanyl acetate sugar moieties with uracil or 6-azauracil with alkyl chains$(C_1-C_3)$ on 5 or 6 position.

• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.338-347
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• 2008

Yeast RAD2, a yeast homolog of human XPG gene, is an essential element of nucleotide excision repair (NER), and its deletion confers UV sensitivity and NER deficiency. 6-Azauracil (6AU) sensitivity of certain rad2 mutants revealed that RAD2 has transcription elongation function. However, the fundamental mechanism by which the rad2 mutations confer 6AU sensitivity was not clearly elucidated yet. Using an insertional mutagenesis, PUF4 gene encoding a yeast pumilio protein was identified as a deletion suppressor of rad2${\Delta}$ 6AU sensitivity. Microarray analysis followed by confirmatory RT-qPCR disclosed that RAD2 and PUF4 regulated expression of HPT1 and URA3. Overexpression of HPT1 and URA3 rescued the 6AU sensitivity of rad2${\Delta}$ and puf4${\Delta}$ mutants. These results indicate that 6AU sensitivity of rad2 mutants is in part ascribed to impaired expression regulation of genes in the nucleotide metabolism. Based on the results, the possible connection between impaired transcription elongation function of RAD2/XPG and Cockayne syndrome via PUF4 is discussed.