Thymidylate synthase, promoter

Thymidylate Synthase Promoter Enhancer Region (TSER)... 

Zinzindohoue F, Ferraz JM, Laurent-Puig P. Thymidylate synthase promoter polymorphism. J Clin Owco/2001 19 3442. 

Lee Y, Shen G, Johnson LP (1999) Complex transcriptional initiation patteren of the thymidylate synthase promoter in mouse tissues. Archiv Biochem Biophys 372 389-392 Leung RK, Ko RC (1997) In vitro effects of Trichinella spirahs on muscle cells. J Helminthol 71 113-118... 

Thymidylate Synthase Gene Promoter Polymorphism and Response to 5-Flurouracil-Based Chemotherapy... 

VlLLAFRANCA E, OKRUZHNOV Y, DOMIN-guez MA et al. Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging after preoperative chemoradiation in rectal cancer. J Clin Oncol 2001 19 1779-1786. 

Morganti M, Ciantelli M, Giglioni B et al. Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in eoloreetal cancers. iiMrJCawcer 2005 41 2176-2183. 

Thymidylate synthase (TS) is a 15,876 base pair gene with seven exons located on chromosome 18p 11.32 (14). To date, the 28 bp promoter region insertion is the most thoroughly studied in pediatric ALL patients. The 28 bp promoter region 3R (repeat) homozygosity rate is 33% in Caucasians, 40% in South Asians, and 67% in Chinese (15). A 6 bp insertion has also been identified in the 3 untranslated region of TS (16). 

Sources of deoxyuridine in DNA include the presence of dUTP because dUMP (the substrate for thymidylate synthase) or dUDP (from ribonucleotide reductase action on UDP) are phosphorylated to the triphosphate. DNA polymerase recognizes these compounds as substrates. Another source is the deamination of deoxycytidine in DNA, promoted by a variety of compounds. If deoxyuridine is on a template strand of the DNA, it will direct the incorporation of an A in the newly made strand of DNA. This will convert a G-C pair to an A-T pair. 

Fluoro-2, 5 -dideoxyuridine-5 -5-thiosulfate (37) was synthesised from 5-fluoro-5 -0-tosylo-2 -deoxyuridine and sodium thiosulfate pentahydrate in ethanol at reflux. This compound is a member of a larger family of analogues of dUMP, dTMP and 5-fluoro-dUMP which have been used to probe interactions with thymidylate synthase. Ethyl chloroformate was shown to be an effective promoter as an alternative to DCC in the preparation of l-[((5)-2-hydroxy-2-oxo-l,4,2-dioxaphosphorinan-5-yl)methyl] cytosine (cyclic HPMPC) from HMPC in large scale quantities and in high isolated yield as well as purity. " ... 

The presence of a 28-bp VNTR in the promoter region of the thymidylate synthase (TYMS) gene has been shown to be associated with changes in in... 

In the Famulok laboratory, a ribozyme was isolated which promotes a reaction corresponding to the first step of the formation of dTMP from dUMP in proteic thymidylate synthases. This ribozyme mediates Michael-adduct formation at a Michael-acceptor substrate. The reaction is accelerated by a factor of nearly 10. The selected ribozyme could be engineered to act in an intermolecular reaction on a substrate tethered to an RNA oligomer. The danonstration of RNA catalysis of this reaction has bearings on the RNA world hypothesis, as well as implications for possible synthetic applications. ... 

---