24 research outputs found
Chromosome and DNA methylation dynamics during meiosis in autotetraploid Arabidopsis arenosa
Variation in chromosome number due to
polyploidy can seriously compromise meiotic stability. In
autopolyploids, the presence of more than two homologous
chromosomes may result in complex pairing patterns
and subsequent anomalous chromosome
segregation. In this context, chromocenter, centromeric,
telomeric and ribosomal DNA locus topology and DNA
methylation patterns were investigated in the natural
autotetraploid, Arabidopsis arenosa. The data show that
homologous chromosome recognition and association
initiates at telomeric domains in premeiotic interphase,
followed by quadrivalent pairing of ribosomal 45S RNA
gene loci (known as NORs) at leptotene. On the other hand, centromeric regions at early leptotene show pairwise
associations rather than associations in fours. These
pairwise associations are maintained throughout prophase
I, and therefore likely to be related to the diploid-like
behavior of A. arenosa chromosomes at metaphase I,
where only bivalents are observed. In anthers, both cells
at somatic interphase as well as at premeiotic interphase
show 5-methylcytosine (5-mC) dispersed throughout the
nucleus, contrasting with a preferential co-localization
with chromocenters observed in vegetative nuclei. These
results show for the first time that nuclear distribution
patterns of 5-mC are simultaneously reshuffled in meiocytes
and anther somatic cells. During prophase I, 5-mC
is detected in extended chromatin fibers and chromocenters
but interestingly is excluded from the NORs what
correlates with the pairing patter
Progressive Telomere Dysfunction Causes Cytokinesis Failure and Leads to the Accumulation of Polyploid Cells
Most cancer cells accumulate genomic abnormalities at a remarkably rapid rate, as they are unable to maintain their chromosome structure and number. Excessively short telomeres, a known source of chromosome instability, are observed in early human-cancer lesions. Besides telomere dysfunction, it has been suggested that a transient phase of polyploidization, in most cases tetraploidization, has a causative role in cancer. Proliferation of tetraploids can gradually generate subtetraploid lineages of unstable cells that might fire the carcinogenic process by promoting further aneuploidy and genomic instability. Given the significance of telomere dysfunction and tetraploidy in the early stages of carcinogenesis, we investigated whether there is a connection between these two important promoters of chromosomal instability. We report that human mammary epithelial cells exhibiting progressive telomere dysfunction, in a pRb deficient and wild-type p53 background, fail to complete the cytoplasmatic cell division due to the persistence of chromatin bridges in the midzone. Flow cytometry together with fluorescence in situ hybridization demonstrated an accumulation of binucleated polyploid cells upon serial passaging cells. Restoration of telomere function through hTERT transduction, which lessens the formation of anaphase bridges by recapping the chromosome ends, rescued the polyploid phenotype. Live-cell imaging revealed that these polyploid cells emerged after abortive cytokinesis due to the persistence of anaphase bridges with large intervening chromatin in the cleavage plane. In agreement with a primary role of anaphase bridge intermediates in the polyploidization process, treatment of HMEC-hTERT cells with bleomycin, which produces chromatin bridges through illegimitate repair, resulted in tetraploid binucleated cells. Taken together, we demonstrate that human epithelial cells exhibiting physiological telomere dysfunction engender tetraploid cells through interference of anaphase bridges with the completion of cytokinesis. These observations shed light on the mechanisms operating during the initial stages of human carcinogenesis, as they provide a link between progressive telomere dysfunction and tetraploidy