Differential effects on the B‐to‐Z transition of Poly(dG‐me5dC) · Poly(dG‐me5dC) Produced by N1‐and N8‐Acetyle Spermidine

Thomas, Thresia; Bloomfield, Victor A.; Canellakis, Zoe N.

doi:10.1002/bip.360240411

Cited by 46 publications

(30 citation statements)

References 14 publications

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“…Acetylation of spermidine and spermine reduces the potency of the polyamine as the positive charge on the amino terminus is partially neutralized [4,65]. Acetylation also marks the polyamine for degradation by polyamine oxidases.…”

Section: Spermidine/spermine Acetyl Transferase (Ssat)mentioning

confidence: 99%

Polyamine metabolism and cancer

Thomas

2003

J Cellular Molecular Medi

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289

213

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Polyamines are aliphatic cations present in all cells. In normal cells, polyamine levels are intricately controlled by biosynthetic and catabolic enzymes. The biosynthetic enzymes are ornithine decarboxylase, S-adenosylmethionine decarboxylase, spermidine synthase, and spermine synthase. The catabolic enzymes include spermidine/spermine acetyltransferase, flavin containing polyamine oxidase, copper containing diamine oxidase, and possibly other amine oxidases. Multiple abnormalities in the control of polyamine metabolism and uptake might be responsible for increased levels of polyamines in cancer cells as compared to that of normal cells. This review is designed to look at the current research in polyamine biosynthesis, catabolism, and transport pathways, enumerate the functions of polyamines, and assess the potential for using polyamine metabolism or function as targets for cancer therapy.

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Section: Spermidine/spermine Acetyl Transferase (Ssat)mentioning

confidence: 99%

Polyamine metabolism and cancer

Thomas

2003

J Cellular Molecular Medi

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289

213

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“…The ability of Z-DNA to undergo further structural organizations including the Iv-DNA form in the presence of Co(NH3)63+ has several important biological implications. With the discovery of physiologically compatible conditions, including the presence of natural polyamines (1,(34)(35)(36) and negative supercoiling (37)(38)(39) in physiologic cation concentrations, it has become evident that Z-DNA has a potential biological function if the right combination of DNA sequence distribution and the microenvironment to provoke the Z-DNA conformation is available. The reported inability of Z-DNA to form nucleosomes under reconstitution conditions (40), however, posed a problem in realizing this potential because the DNA in the cell is tightly packaged in the form of chromatin.…”

Section: Discussonmentioning

confidence: 99%

Direct evidence for the presence of left-handed conformation in a supramolecular assembly of polynucleotides

Thomas¹

1989

Nucl Acids Res

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Hexammine cobalt(lIl) chloride (Co(NH3)63+) provokes a B-DNA -4 Z-DNA -+ P-DNA conformational transition in poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC). The circular dichroism spectrum of '-DNA is characterized by a manyfold increase of positive ellipticity in the range of 300-225 nm and the complete absence of a negative peak. In order to ascertain the helical handedness of '-DNA, we used a recently developed enzyme immunoassay technique. This method consisted of treating the polynucleotides with Co(NH3)63+ to convert them to the Z-or '-DNA forms and immobilizing these conformations on a microtiter plate.The plates were subsequently treated with a monoclonal anti-Z-DNA antibody Z22, alkaline phosphatase conjugated, affinity purified immunoglobulins, and the phosphatase substrate. The enzyme-substrate reaction was monitored by reading the absorbance at 405 nm with a microplate autoreader. The monoclonal anti-Z-DNA antibody had no reactivity to the B-DNA form, but bound strongly to both the Z-and '-DNA forms, showing that Co(NH3)63+-induced '-DNA form of the polynucleotides exists in the left-handed Z-DNA conformation. INTRODQUCTIONMultivalent ions like Co(NH3)63+ and Ru(NH3)63+ are excellent promoters of the transition of poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) from their usual right-handed B-DNA form to the left-handed Z-DNA conformation at micromolar concentrations of these counterions (1-4). Increasing concentrations of Co(NH3)63+ are also known to provoke a supramolecular organization of the polynucleotides from the Z-DNA form to a '-DNA form (5-6). The '-DNA form is a believed to be a twisted, tightly packaged assembly of DNA.Several agents, including polylysine, spermine, ethylene glycol, and salt are known to convert native DNAs to the '-DNA form (7-9). The formation of this structural form of DNA is characterized by a large (10-to 100-fold) increase in the intensity of the molar ellipticity of DNA in circular dichroism (CD) spectroscopic measurements. This property has presented a basic problem in interpreting the CD spectrum of '-DNA and assigning its helical handedness. This uncertainty has recently led to the conclusion that '-DNA is the end product in the

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“…9 Other explanations for this observed effect as well as new experimental data not showing any base-composition effects have been put forward. 10 Many modifications of the natural polyamines like charge stripping, 11,12 variation in alkyl-chain lengths, [13][14][15][16][17] and added side chains 12,18,19 have been studied experimentally throughout the years. Of particular relevance for the present work are some recent nmr studies of oligonucleotides with polyamines that have been performed by Wemmer et al, 20 Banville et al, 21 and by Andreasson et al from this laboratory.…”

Section: Introductionmentioning

confidence: 99%