Glycosylases synthesis

DNA glycosylases 971 AP site 971 AP endonucleases 972 DNA photolyases 974 recombinational DNA repair 976 error-prone translesion DNA synthesis 976 SOS response 976 homologous genetic recombination 978... 

Removal of abnormal bases Abnormal bases, such as uracil, which can occur in DNA either by deamination of cytosine or improper incorporation of dUTP instead of dTTP during DNA synthesis, are recognized by specific glycosylases that hydrolytically cleave them from the deoxyribose-phosphate backbone of the strand. This leaves an apyrimidinic site (or apurinic, if a purine was removed), referred to as an AP-site. 

The concluding steps of BER involve DNA synthesis to replace the damaged nucleotide and ligation. If the glycosylase has an associated AP lyase activity, it can generate a 3 -a, [) unsaturated aldehyde (Figure 23.7). This residue must be pro-... 

The oxidised abasic site (146) was generated in ODNs by incorporation of 4 -azido-2 -dUTP. ssDNA containing 4 -azido-dU treated with uracil DNA glycosylase generates the lesion (146), and characterisation of DNA containing (146) has been carried out. It has also been generated in situ by incorporation of a bis-O-veratryl modified nucleoside, which is then converted to (146) on photolysis. The translesion synthesis of (146) by Klenow fragment demonstrated that, like the (145) lesion, dA and dG are principally incorporated opposite the C4 -oxidised lesion. ... 

Thymidylale synthase, 498,502 Thymine DIVA glycosylase. 894 ThyrogtobuLin, 7JI-732 Thyroid gland diseases, 306 tcgulation, 735 Thyroid hormone, 585, 7.31 action, 588-589 deiodinases, 734-735 hoimnnal effects of, 735-736 hyperthyroidism, 736 hypothyroidism, 736 synthesis, 731-734... 

N-glycosylase that removes U from DNA. Figure 27-29 summarizes the pathway for TTP synthesis. 

The excision of nucleic acid bases by hydrolases can be both a repair mechanism for the host and an offensive weapon by competitors. There is a whole array of DNA repair glycosylases, some of which are merely hydrolases, others of which have an associated lyase activity.Catalysing a similar reaction are the proteins, formed in the seeds of many plants, which hydrolyse a ribosyl-adenine bond in the sequence GAGA loop region of the 28S RNA, thus shutting down protein synthesis.No direct determination of reaction stereochemistry has been carried out for either class of enzyme, nor is an X-ray structure of an enzyme-substrate-analogue complex available, but the crystal structures so far available suggest inversion. 

The life and work of Edward J. Hehre, a pioneer in our knowledge of the mechanism of action of glycosylase enzymes, is the subject of the article by Brewer (New York). It is noted with regret the passing on February 23, 2004, of Aleskander Zamojski, who contributed in Volume 40 an article on the synthesis of sugars from noncarbohydrate sources, and on July 31, 2004, of Jacques van Boom (Leiden), who made important contributions to carbohydrate synthesis and to glycobiology. 

Recent studies have revealed that marine viruses encode unexpected and novel proteins which would not be expected to occur within a virus genome. For example, the giant algal viruses have been shown to encode novel glycosylases, potassium pumps, and a pathway for the synthesis of complex sphingolipids. This biochemical diversity indicates that marine viruses could be a rich source for exploitation in the future for new types of carbohydrate and lipid as well as new proteins and enzymes. 

CHO, Chinese hamster ovary CYP, cytochrome P450 Endo III, endonuclease III Fpg, formamido-pyrimidine-DNA-glycosylase GST, glutathione S-transferase ID, International units MOCK, Madin-Darby canine kidney S9, 9000 x g supernatant from rat liver SCE, sister chromatid exchange LIDS, unscheduled DNA synthesis. 

---