The Repair Enzyme Uracil-dna-glycosylase: Study of the Mechanism of Functioning Using Modified Analogues of Dna

Uracil-DNA-glycosylase (UDG) is the first enzyme in the base excision repair pathway for removal of uracil in DNA. The disturbance of reparation system results in occurrence of a number of diseases, including various kinds of a cancer. Uracil (Ura) in DNA may result from incorporation of dUMP instead of dTMP or from spontaneous deamination of cytosine in DNA. The majority of organisms delete the erroneous uracil bases from DNA by UDG, which cleaves N-glycosylic bond between this base and the deoxyribose residue to give an apyrimidinic site [1]. UDG sequences from different sources (human placenta, E.coli, Streptococcus pneumonia, different herpes viruses etc) are closely related. They are small single-polypeptide chain enzymes with no cofactor requirement [2]. The aim of the present work is: (i) to summarized our biochemical data which was obtained for UDG from human placenta by using synthetic substrate analogs and characterize UDG-DNA interaction in solution; (ii) to compare our results with X-ray data for complex of mutant non-active UDG with 2 ′ -deoxyuridine (dU)-containing DNA duplex [3].