The regulation of telomerase activity is likely to be a complex issue, involving the transcriptional activity of the telomerase RNA component gene, (hTR) and the telomerase catalytic component gene (hTRT), as well as the interaction of telomerase with other telomere-associated prote ...

Cytochrome P450 (CYP) is comprosed of a family of hemeprotein monooxygenases that catalyze reactions as diverse as the biosynthesis of steroid hormones, metabolism of fat-soluble vitamins, oxidation of unsaturated fatty acids, and metabolism of drugs, pollutants, and other xenob ...

This chapter describes an approach to destroying malignant cells by effectively changing the tumor phenotype through the delivery of Escherichia coli purine nucleo-side phosphorylase (PNP). In the presence of nucleoside prodrugs, this nonhuman enzyme in purine metabolism caus ...

The development of enzyme-prodrug approaches for targeted treatment of human tumors has gained momentum in the last decade, especially with the advent of antibodies, viral vectors, and nonviral delivery systems that might be suitable for use in vivo. However, relatively few novel enzyme ...

Thymidine phosphorylase (E.C. 2.4.2.4) (TP), also described as the angiogenic platelet-derived endothelial cell growth factor (PD-ECGF) (1–4), is a homodimeric enzyme with a monomeric molecular mass of about 55 kDa (5,6) that phosphorolytically cleaves thymidine to yield thymine and de ...

With recent progress in determining the crystal structures of type I and type II topoisomerases (topo I and topo II, respectively) (1,2), an understanding of the binding of DNA-cleavage-inducing inhibitors at the atomic level is within reach. A very useful approach for investigating the natu ...

DNA topoisomerase I and II catalyze topological changes of DNA by transient breakage of the nucleic acid backbone. Topoisomerase I transiently cleaves one DNA strand and allows the passage of single-stranded DNA through the generated nick, whereas topoisomerase II introduces a trans ...

Topoisomerase enzymes catalyze changes in DNA topology by a concerted breakage and reunion of the DNA phosphodiester backbone (1,2). This process occurs via sequential transesterification reactions involving a tyrosyl hydroxyl group present in the active site of the enzyme. A novel a ...

Type I DNA topoisomerases change the linking number of supercoiled DNA by carrying out orcheastrated cleavage and ligation reactions involving phosphodiester bonds. Strand cleavage is not the result of phosphodiester hydrolysis, but the result of transesterification of an acti ...

DNA topoisomerases I and II (topo I and topo II) are ubiquitous nuclear enzymes that regulate DNA topology by breaking and resealing one or both strands of a DNA duplex. Topoisomerase I makes a single-stranded break in a DNA duplex, mediates passage of the intact strand through the break, and then resea ...

The DNA unwinding effect of a drug, derived from either DNA intercalation or groove binding, represents a warning signal for its possible link to side effects or toxicity. DNA unwinding results in a lengthening of the double helix. This increase in length can be detected by physicochemical (such as ...

The interactions of small molecules with nucleic acids have provoked considerable interest in the field of antitumor drug design over the past three decades; however, critical information linking the physical-chemical properties associated with these complexes with their bio ...

One of the most powerful methods for investigating the molecular mechanism of drug action is the use of radioligand binding technique. The method allows investigators to pinpoint the direct target of the drug, and the nature of the interaction in terms of binding affinity, specificity, and coo ...

Fluoroquinolone antibacterials rapidly kill susceptible bacteria at clinically relevant drug concentrations; all evidence indicates that these drugs exert their lethality on Escherichia coli by inhibiting the normal function of the DNA gyrase (a bacterial topoisomerase ...

DNA Topoisomerases (topos) are ubiquitous enzymes that catalyze the breakage and rejoining of the DNA phosphodiester backbone, which together with an intervening strand passage event, allow this these enzymes to alter DNA topology (1,2). Intermediates in the strand passage reaction ...

Type I topoisomerases catalyze topological changes in duplex DNA by reversibly nicking one strand, whereas type II enzymes catalyze the transient breakage of both strands simultaneously. The type I enzymes alter the linking number of covalently closed circular DNA in steps of one, presu ...

Flow cytometry is a laser-based technique used for the quantitation of specific intracellular and extracellular properties of cells, bacteria, or other biological particles. It is unique in its ability to perform simultaneous multiparameter analysis and to sort single cell types fr ...

Topoisomerase II is a requisite enzyme that cleaves both strands of double-stranded DNA, allowing for passage of a second DNA duplex, resulting in the unwinding of chromosomal DNA. Topo II is covalently bound to the 5′-end of the cleaved DNA in a reversible reaction. However, treatment with numero ...

A variety of flow cytometric methods have been developed over the past 25 yr to study how treatment with chemotherapeutic agents affects cell-cycle progression. One of the most commonly used measurements relies on a singletime analysis of the DNA distribution of a cell population (1). This ana ...

The physiology of bacterial DNA topoisomerases can be studied by examining how perturbation of intracellular enzyme activities affects the structure of extracted nucleoids. Since the few DNA nicks that occur when nucleoids are isolated (1,2) are localized by the presence of 50–100 barr ...