The minor-groove binding DNA-ligands netropsin, distamycin A and berenil cause polyploidisation via impairment of the G2 phase of the cell cycle.
Distamycin A, netropsin and berenil are known to cause undercondensation of heterochromatic regions of metaphase chromosomes. These ligands interfere with DNA curvature by binding to the minor groove of the DNA. Whereas the effects of these ligands upon chromatin structure are well established, little is known about their possible interference with cell cycle progression. We show that the presence of these DNA-ligands causes protracted cell growth consisting of a prolongation of the G1 phase of the cell cycle along with arrest in the G2 compartment. Concomitant with these cell kinetic disturbances the DNA ligands cause increased polyploidisation. These observations suggest that the DNA-minor groove may play an important role in progression through the G2 phase and proper mitotic transit.
Department of Human Genetics, University of Würzburg, West Germany.
M
M
Poot
K
K
Kausch
J
J
Köhler
T
T
Haaf
H
H
Hoehn
D000578:Amidines / Q000494:pharmacology*; D006690:Bisbenzimidazole; D001973:Bromodeoxyuridine / Q000378:metabolism; D004247:DNA / Q000187:drug effects*; D004133:Diminazene / Q000031:analogs & derivatives / Q000494:pharmacology*; D004214:Distamycins / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D005434:Flow Cytometry; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007399:Interphase / Q000187:drug effects; D009429:Netropsin / Q000494:pharmacology*; D011123:Polyploidy; D011758:Pyrroles / Q000494:pharmacology*
D000578:Amidines; D004214:Distamycins; D006146:Guanidines; D011758:Pyrroles; D009429:Netropsin; C030000:stallimycin; D004247:DNA; D001973:Bromodeoxyuridine; C003915:diminazene aceturate; D006690:Bisbenzimidazole; D004133:Diminazene