Interaction of anthracyclines with DNA and chromosomes

Abstract

Daunomycin and adriamycin were previously found to produce Q-like banding patterns on chromosomes. The interaction of several anthracyclines with both natural and synthetic DNAs and chromosomes has been investigated in more detail. Daunomycin fluorescence is almost completely quenched by natural DNAs with varying base composition from 31 to 72% G-C and by the alternating polymer poly-d(G-C).poly-d(G-C). In contrast, daunomycin fluorescence is quenched by only 50% when the dye interacts with synthetic A-T polymers. Thus, differential quenching of daunomycin fluorescence can account for the production of bright bands at contiguous A-T sequences along the chromosome. Slight differences in fluorescence quenching between the repeating and homopolymeric A-T duplex DNAs were observed which can be attributed to differences in affinity of daunomycin for these DNAs. The aminosugar moiety of daunomycin, daunosamine, increases the binding of daunomycin to DNA and also enhances chromosome banding.--Nogalamycin, which displays no differential quenching with the different DNAs in solution, also fails to produce bands on chromosomes.--These findings suggest that non-random nucleotide sequence arrangements along the chromosome are a basic determinant for dye interaction to produce the observed banding patterns. Specific banding procedures may determine the accessibility of these sites within the chromosomal DNA.

Evidence of the differentiated structural arrangement of constitutive heterochromatin between two populations of Astyanax scabripinnis (Pisces, Characidae)

“…The GC clusters of this putative family might be exposed on the chromosomes of the Centenário population, while the 2n = 48 Marrecas population may possess inverse structural organization that ex- Mantovani et al 539 poses the As51 sequences. These assumptions support the presumed influence of the non-random arrangement of nucleotide sequences based on the fluorescent patterns obtained with specific fluorochromes (Johnston et al, 1978;Saitoh and Laemmli, 1994), and again support the proposition that the distal heterochromatins of the Centenário and Marrecas populations are structurally dissimilar. The presence of a GC-rich satellite sequence in the distal heterochromatin of the Centenário population could be checked using the method of Rab et al (1996), which employs differential denaturation based on the fact that GC-rich clusters have higher thermal stability.…”

“…Although DAPI is known to bind to both GC and AT base pairs its fluorescence is significantly enhanced by AT-rich regions (Lin et al, 1977) so that the AT base content of the As51 satellite DNA (59%) may be insufficient to produce DAPI-positive fluorescence, as has already been described for daunomycin, an antibiotic that only fluoresces when bound to highly AT-rich (65%) DNAs (Comings and Drets, 1976;Comings, 1978;Johnston et al, 1978). Moreover, when discussing other fluorescent compounds, Comings and Drets (1976) pointed out that lack of fluorescence in heterochromatic regions may be due to the effect of chromosomal proteins on access of the fluorochromes to satellite DNA, while Saitoh and Laemmli (1994) stated that the structural organization of the chromosomal heterochromatic sequences may also be a factor in whether or not fluorescence occurs.…”

Daunomycin, an antitumor DNA intercalator, influences histone–DNA interactions

“…This unexpectedly low intensity of nuclear fluorescence is likely to reflect a limited access and a reduced ability of daunomycin to bind DNA in situ, as well as quenching of daunomycin fluorescence upon intercalation into DNA. 9,10 Following formaldehyde fixation, the drug was released from the Golgi apparatus and was bound by nuclear DNA (Fig. 1D-G).…”

Colocalization of repetitive DNAs and silencing of major rRNA genes. A case report of the fish <i>Astyanax janeiroensis</i>

“…Comings and Drets (1976), Comings (1978) and Johnston et al (1978) reported that the antibiotic Daunomycin is able to show fluorescence only when the AT-content exceeds 65% of the DNA composition. It is possible that the low number of AT-rich sites usually detected in fish species may be related to the lack of AT-rich repetitive DNA sequences above such a threshold.…”