PubMed Health⌕ Search

PubMed · 10592317

Chromosome aberrations induced by aphidicolin.

Abstract

The expression of aphidicolin (apc)-produced common fragile sites and chromosome aberrations observed 24 h after apc treatment was studied in a normal individual. The chromosome lesions (gaps and breaks) induced by apc are expressed as full chromosomal aberrations in later cell divisions. We compared chromosome rearrangements or anomalies induced by apc (detected in 45.4% of metaphases analyzed) with those present in human neoplasia or involved in primate evolution. We found that 55.7% of deletions observed in our study coincided with deletions implicated in several types of neoplasia. However, none of 49 translocations observed in our study coincided with those described as recurrently associated with human neoplasia, probably due to their unbalanced nature. When chromosome aberrations detected in our study (only deletions and inversions were taken into account) were compared to those involved in primate evolution, we found a low rate of coincidence. The low coincidence between chromosome alterations in neoplasia and evolution and those observed in our study could be explained because we analyzed chromosome alterations that had not been selected, whereas those present in chromosome evolution and in neoplasia had been subjected to a selection process.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

F Carme, M Rosa, E Josep. 1999-11-29. Chromosome aberrations induced by aphidicolin.. https://doi.org/10.1016/s0027-5107(99)00125-6

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Influence of IBA and aphidicolin on DNA synthesis and adventitious root regeneration from Malus 'Jork 9' stem discs.

Adventitious root formation in Malus 'Jork 9' stem discs was studied through temporarily blocking DNA synthesis by application of aphidicolin (AD). Higher number of roots per disc (8.4) after 21 days of cultivation were formed after a 24-h pulse of 15 microM AD, compared to control without AD application (6.7), with significantly more roots (3.7) already appearing at day 7, compared to 1.5 roots on the control. The promotive effect of AD on rooting was lower at 5 microM, while a concentration of 30 microM was slightly inhibitory. Results show that DNA synthesis is effectively blocked by AD, and this blockage is overcome after AD withdrawal. The data indicate that AD treatment influences cell divisions, thereby, might synchronise root initiation. The effects of different treatments with and without AD were studied at the cellular level by visualising DNA replication through BrdU-labelling. BrdU labelling further revealed temporal changes in the competence of the explants to respond to applied IBA. Thus, it is shown that the proportion of replicating nuclei present during 28-32 h is significantly increased in the split IBA treatment (0-4 h and 28-32 h; treatment C3), compared with a single IBA application during 0-8 h (treatment C3.1).

Aphidicolin↗

Arabidopsis WEE1 kinase controls cell cycle arrest in response to activation of the DNA integrity checkpoint.

Upon the incidence of DNA stress, the ataxia telangiectasia-mutated (ATM) and Rad3-related (ATR) signaling kinases activate a transient cell cycle arrest that allows cells to repair DNA before proceeding into mitosis. Although the ATM-ATR pathway is highly conserved over species, the mechanisms by which plant cells stop their cell cycle in response to the loss of genome integrity are unclear. We demonstrate that the cell cycle regulatory WEE1 kinase gene of Arabidopsis thaliana is transcriptionally activated upon the cessation of DNA replication or DNA damage in an ATR- or ATM-dependent manner, respectively. In accordance with a role for WEE1 in DNA stress signaling, WEE1-deficient plants showed no obvious cell division or endoreduplication phenotype when grown under nonstress conditions but were hypersensitive to agents that impair DNA replication. Induced WEE1 expression inhibited plant growth by arresting dividing cells in the G2-phase of the cell cycle. We conclude that the plant WEE1 gene is not rate-limiting for cycle progression under normal growth conditions but is a critical target of the ATR-ATM signaling cascades that inhibit the cell cycle upon activation of the DNA integrity checkpoints, coupling mitosis to DNA repair in cells that suffer DNA damage.

Aphidicolin↗

Osteopontin localizes to the nucleus of 293 cells and associates with polo-like kinase-1.

Osteopontin (OPN) is a secreted phosphoprotein involved in cellular proliferation and associated with tumor progression. Although an intracellular form of OPN has been described, its function remains unknown. In this study, a novel nuclear location for intracellular OPN and a correlation with cell division were demonstrated. OPN distinctly localized to the nucleus in a subset of transiently transfected human embryonic kidney 293 cells. Immunoblotting confirmed the nuclear location of native OPN, and results from immunofluorescence studies suggested an association between nuclear OPN and cell cycle progression. Flow cytometry revealed that nuclear and cellular OPN content rose significantly during the S and G(2)/M phases, respectively. Treatment of cells with the DNA polymerase inhibitor aphidicolin prevented cell cycling and greatly reduced cellular OPN content. The intracellular location of OPN coincided with polo-like kinase-1 (Plk-1), a member of the polo-like kinase family, which, in part through their regulation of centrosome-related events, are integral to successful cellular mitosis. OPN and Plk-1 were coimmunoprecipitated from nuclear, but not cystoslic, extracts, demonstrating an interaction that is limited to the nucleus, presumably during mitosis. Deletion of the COOH terminus of OPN militated against nuclear localization and Plk-1 interaction. Elevated expression of OPN was also associated with an increase in the number of multinucleate 293 cells, whereas transfection of the COOH-terminal-deleted OPN decreased the percentage of multinucleate cells below basal levels. These findings implicate intranuclear OPN as a participant in the process of cell duplication.

Aphidicolin↗