The telomeric region is excluded from nucleosomal fragmentation during apoptosis, but the bulk nuclear chromatin is randomly degraded

Abstract

Characteristic steps during cellular apoptosis are the induction of chromatin condensation and subsequent DNA fragmentation, finally leading to the formation of oligomers of nucleosomes. We have examined the kinetics and local distribution of this nucleosomal fragmentation within different genomic regions. For the induction of apoptosis, HL60 cells were treated with the water-soluble camptothecin derivative topotecan (a topoisomerase I inhibitor). The genomic origin of the fragments was analysed by Southern blot hybridisation of the cleaved DNA. In these experiments we observed similar hybridisation patterns of the fragmented DNA, indicating a random and synchronous cleavage of the nuclear chromatin. However, hybridisation with a telomeric probe revealed that, in contrast to the other analysed genomic regions, the telomeric chromatin was not cleaved into nucleosomal fragments despite our observation that the telomeric DNA in HL60 cells is organised in nucleosomes. We determined just a minor shortening of the telomeric repeats early during apoptosis. These observations suggest that telomeric chromatin is excluded from internucleosomal cleavage during apoptosis.

p-Methoxycinnamic acid, an active phenylpropanoid induces mitochondrial mediated apoptosis in HCT-116 human colon adenocarcinoma cell line

“…Previous scientific studies have reported that DNA fragmentation is a late event in apoptosis and large fragments are observed in early stages (Schliephacke et al, 2004). The obtained results revealed a strong proapoptotic characteristic feature of p-MCA.…”

Changes in lamina structure are followed by spatial reorganization of heterochromatic regions in caspase-8-activated human mesenchymal stem cells

“…The biological function for telomere aggregation is not yet known. Recent studies, using biochemical approaches, show that telomeric regions are excluded from internucleosomal fragmentation during apoptosis (Schliephacke et al, 2004). Thus, it is possible that, during the onset of apoptosis, telomere aggregation protects these heterochromatic regions from degradation.…”

Birth and death: Evidence for the same biologic clock

“…16,18,19 Telomere lengths vary significantly between chromosomes, between organs in the body, and between different species. 11,16 For example, average telomere lengths in human cells are 15-20 kb 11,13,20 vs 25-150 kb in mouse cells; and with the lengths varying even between different mouse strains. 21,22 Based on the evaluation of telomeres in 43 mammalian species, Gomes et al 23 observed that the lengths are inversely related life span, leading to the hypothesis that shorter telomeres in longer living organisms provide a mechanism to count cell divisions and to utilize replicative aging as a tumor suppression mechanism.…”