Search results for "Genomic Instability"
showing 5 items of 45 documents
Tupaia small RNAs provide insights into function and evolution of RNAi-based transposon defense in mammals
2015
Argonaute proteins comprising Piwi-like and Argonaute-like proteins and their guiding small RNAs combat mobile DNA on the transcriptional and post-transcriptional level. While Piwi-like proteins and associated piRNAs are generally restricted to the germline, Argonaute-like proteins and siRNAs have been linked with transposon control in the germline as well as in the soma. Intriguingly, evolution has realized distinct Argonaute subfunctionalization patterns in different species but our knowledge about mammalian RNA interference pathways relies mainly on findings from the mouse model. However, mice differ from other mammals by absence of functional Piwil3 and expression of an oocyte-specific …
The dual role of p53: DNA protection and antioxidant.
2011
The classical functions of p53 protein are those related to its role on DNA damage, cell growth arrest, senescence and apoptosis. For this reason it is called 'the guardian of the genome' and is considered one of the most important players in the development of cancer. However, more recently it has been show that p53 is not only involved in cancer, but also in ageing. p53 is stimulated by stress, which in turn results in the activation of a wide range of transcriptional targets. Low-intensity stress will activate p53 in a manner which results in antioxidant response, thus protecting against ageing because of its antioxidant function. On the contrary, high-intensity activation of p53 will re…
Persistent genomic instability by arsenic exposure in V79 Chinese hamster cells
2006
Previously, we demonstrated that acute treatment with arsenic leads mammalian cells to exhibit persistent chromosomal instability and DNA hypomethylation, by performing investigations after about 2 months of subculturing. In order to evaluate quantitatively the continuing instability during the expanded growth, we carried out cytogenetic, morphologic and molecular analyses immediately after exposure and every week up to 112 cell generations. Briefly, V79 Chinese hamster cells were treated with 10 µM sodium arsenite (SA) for 24h; at the end of exposure, mitotic rounded-up cells were harvested by shake-off and allowed to grow in drug-free medium. The instability markers, micronucleated and mu…
Persistent dysregulation of DNA methylation in cells with arsenic-induced genomic instability
2009
The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. In previous studies long-term progression of chromosomal instability was typified by increasing aneuploidy in Chinese hamster V79 and human keratinocyte cells treated with arsenite for a 24 hr exposure period followed by growth in arsenic-free medium for 40-120 cell generations. In the current study the role of progressive DNA methylation changes was evaluated in long-term cell cultures after brief arsenite treatments as above. We have found altered genomic methylation patterns in cells that were briefly exposed to arsenic with evidence for widespread dysregulation of CpG methylati…
Long-term exposure to submicromolar arsenite induces bypass of the spindle assembly checkpoint in mammalian cells
2008
Mitosis is regulated by checkpoints that delay mitotic progression when chromosome segregation errors occur. Inaccuracy in checkpoint processes can lead to chromosome instability both in number and structure (CIN). Arsenic is reported to induce CIN by perturbing mitotic spindles and checkpoints, however, its carcinogenic mechanisms are poorly understood. We previously studied the long-term progression of chromosomal instability in V79 cells treated acutely with arsenite (10 M, 24 hr) followed by growth in arsenic-free medium for 120 cell generations, and found time-dependent increase of aneuploid cells. Here, we treated V79-derived G12 cells with sub-lethal doses (0.1-1.0 µM) of arsenite f…