Preferential Accumulation of Single-Stranded Regions in Telomeres of Human Fibroblasts

Petersen, Simone; Saretzki, Gabriele; Zglinicki, Thomas von

doi:10.1006/excr.1997.3893

Cited by 389 publications

(331 citation statements)

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“…The generation of single stranded fragments within telomeres contributes signi®cantly to telomere shortening (Makarov et al, 1997;Sitte et al, 1998;Petersen et al, 1998). The data presented here suggest yet another role: the occurrence of telomeric single stranded DNA, possibly above a certain threshold in length and/or amount, might act as trigger of the p53-dependent cell cycle arrest.…”

Section: Discussionmentioning

confidence: 62%

“…Single stranded fragments are produced in telomeres under mild oxidative stress (von Zglinicki et al, 1995;Petersen et al, 1998). Moreover, telomeres accumulate single-strand damage even under standard cell culture conditions (Sitte et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Single stranded regions accumulate speci®cally in telomeres of human ®broblast (von Zglinicki et al, 1995, Petersen et al, 1998. In contrast to the bulk of the genome, telomeric single-strand damage is less repaired.…”

Section: Oxidative Stress Induces Single Stranded Regions In Telomeresmentioning

confidence: 99%

“…The mean telomeric restriction fragment length (TRF) and the amount of telomere-speci®c single strand damage were measured as described (von Zglinicki et al, 1995;Sitte et al, 1998;Petersen et al, 1998). Brie¯y, cells were embedded in agarose plugs at a concentration of 5610 5 cells per plug and digested with proteinase K. The DNA in the plugs was restricted to completion with HinfI and subjected to pulsed ®eld gel electrophoresis under conditions optimized to resolve a size range of 2 ± 30 kb.…”

Section: P53 Levelsmentioning

confidence: 99%

“…Terminal overhangs of the Grich strand were demonstrated to exist in both immortal cells and ®broblasts (Makarov et al, 1997). Single stranded damage accumulates preferentially in telomeres of human ®broblasts (Petersen et al, 1998). During DNA replication, telomeric single stranded damage is converted into shortened telomeres (Sitte et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

et al. 1999

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It has been repeatedly suspected that telomere shortening might be one possible trigger of the p53-dependent cell cycle arrest, although the mechanism of this arrest remained unclear. Telomeres in human cells under mild oxidative stress accumulate single-strand damage faster than interstitial repetitive sequences. In MRC-5 ®bro-blasts and U87 glioblastoma cells, which both express wild-type p53, oxidative stress-mediated production of single-strand damage in telomeres is concomitant to the accumulation of p53 and p21 and to cell cycle arrest. This response can be modeled by treatment of cells with short single stranded telomeric G-rich DNA fragments. The arrest is transient in U87 cells. Recovery from it is accompanied by up-regulation of telomerase activity and elongation of telomeres. Overexpression of mutated p53 is su cient to reverse the phenotype of inhibition as well as the delayed activation of telomerase. These data suggest that the production of G-rich single stranded fragments during the course of telomere shortening is su cient to trigger a p53 dependent cell cycle arrest.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Oxidative Stress Induces Single Stranded Regions In Telomeresmentioning

confidence: 99%

Section: P53 Levelsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

et al. 1999

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Telomerase activity and telomere detection during early bovine development

Betts

King

1999

Dev. Genet.

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Mitochondrial dysfunction and cell senescence: deciphering a complex relationship

2019

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Cellular senescence and mitochondrial dysfunction have both been defined as classical hallmarks of the ageing process. Here, we review the intricate relationship between the two. In the context of ageing, it is now well regarded that cellular senescence is a key driver in both ageing and the onset of a number of age‐related pathologies. Emerging evidence has pinpointed mitochondria as one of the key modulators in the development of the senescence phenotype, particularly the pro‐inflammatory senescence associated secretory phenotype (SASP). This review focuses on the contribution of homeostatic mechanisms, as well as of reactive oxygen species and mitochondrial metabolites in the senescence programme. Furthermore, we discuss emerging pathways and mitochondrial‐mediated mechanisms that may be influencing the SASP and, subsequently, explore how these may be exploited to open up new therapeutic avenues.

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Preferential Accumulation of Single-Stranded Regions in Telomeres of Human Fibroblasts

Cited by 389 publications

References 32 publications

Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments

Telomerase activity and telomere detection during early bovine development

Mitochondrial dysfunction and cell senescence: deciphering a complex relationship

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