Cellular senescence and DNA repair

Lou, Zhenkun; Chen, Junjie

doi:10.1016/j.yexcr.2006.06.009

Cited by 65 publications

(50 citation statements)

References 53 publications

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“…In the autonomous pathways model, the DNA damagesignaling network activates DNA repair and cell death simultaneously and automatically, which is consistent with the current evidence [2,3,[7][8][9][10][11][12][13][14][15][16][17]. In this review, we will examine these two conceptual models for their capacity to explain DNA damage-induced cell death in the developing central nervous system (CNS) of rodents.…”

Section: Autonomous Pathwayssupporting

confidence: 65%

“…Unfortunately, mitotic death inferred from clonogenic survival assays does not distinguish between (a) the actual death of damaged cells resulting from programmed apoptosis/necrosis and (b) irreversible growth arrest that does not involve cell death [16]. Mitotic death may also describe mitotic catastrophe, which is a consequence of defects in G2/M and spindle checkpoint responses [10,13,14].…”

Section: Activation Of Caspase-independent Apoptosismentioning

confidence: 99%

“…Generally speaking, cell death is a delayed response to DNA damage, resulting in elimination of the damaged cell ( Figure 1). The cell-protective and cell-destructive responses to DNA damage are downstream of a common signal transduction network that has been studied intensively in recent years ( Figure 1) (reviewed in Huen and Chen, in this issue) [2,3,[7][8][9][10][11][12][13][14][15][16][17]. While most protein components of this signaling network have been identified, the current knowledge does not explain when and why a damaged cell will choose to die.…”

Section: Introductionmentioning

confidence: 99%

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DNA damage-induced cell death: lessons from the central nervous system

2007

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npg DNA damage can, but does not always, induce cell death. While several pathways linking DNA damage signals to mitochondria-dependent and -independent death machineries have been elucidated, the connectivity of these pathways is subject to regulation by multiple other factors that are not well understood. We have proposed two conceptual models to explain the delayed and variable cell death response to DNA damage: integrative surveillance versus autonomous pathways. In this review, we discuss how these two models may explain the in vivo regulation of cell death induced by ionizing radiation (IR) in the developing central nervous system, where the death response is regulated by radiation dose, cell cycle status and neuronal development.

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Section: Autonomous Pathwayssupporting

confidence: 65%

Section: Activation Of Caspase-independent Apoptosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA damage-induced cell death: lessons from the central nervous system

2007

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“…TIFs are similar in appearance and protein content to the foci induced at DSBs, and they produce similar downstream effects (e.g. cell cycle arrest, senescence and/or cell death) [38][39][40][41][42].…”

Section: Telomerase Expression and Dysfunctional Telomeresmentioning

confidence: 95%

ATM-like kinases and regulation of telomerase: lessons from yeast and mammals

Sabourin

Zakian

2008

Trends in Cell Biology

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Telomeres, the essential structures at the ends of eukaryotic chromosomes, are composed of G-rich DNA and asociated proteins. These structures are crucial for the integrity of the genome, because they protect chromosome ends from degradation and distinguish natural ends from chromosomal breaks. The complete replication of telomeres requires a telomere-dedicated reverse transcriptase called telomerase. Paradoxically, proteins that promote the very activities against which telomeres protect, namely DNA repair, recombination and checkpoint activation, are integral to both telomeric chromatin and telomere elongation. This review focuses on recent findings that shed light on the roles of ATM-like kinases and other checkpoint and repair proteins in telomere maintenance, replication and checkpoint signaling.

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“…The rate of telomere attrition is slower in long-lived mammals compared with short-lived ones (8). Senescent cells accumulate with increasing age in vivo (9) and are thought to play an important role in organismal aging (10), which is characterized by physiologic and metabolic decline (4) and increasing susceptibility to several diseases associated with death (11). Thus, it is likely that telomere shortening may be mechanistically linked to organismal lifespan.…”

mentioning

confidence: 99%

Telomere length is paternally inherited and is associated with parental lifespan

Njajou

Cawthon

Damcott

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

331

254

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Telomere length (TL) is emerging as a biomarker for aging and survival. To evaluate factors influencing this trait, we measured TL in a large homogeneous population, estimated the heritability (h 2 ), and tested for parental effects on TL variation. Our sample included 356 men and 551 women, aged 18 -92 years, from large Amish families. Mean TL in leukocytes was measured by quantitative PCR (mean: 6,198 ؎ 1,696 bp). The h 2 of TL was 0.44 ؎ 0.06 (P < 0.001), after adjusting for age, sex, and TL assay batch. As expected, TL was negatively correlated with age (r ‫؍‬ ؊0.40; P < 0.001). There was no significant difference in TL between men and women, consistent with our previous findings that Amish men lived as long as Amish women. There was a stronger and positive correlation and association between TL in the offspring and paternal TL (r ‫؍‬ 0.46, P < 0.001; ␤ ‫؍‬ 0.22, P ‫؍‬ 0.006) than offspring and maternal TL (r ‫؍‬ 0.18, P ‫؍‬ 0.04; ␤ ‫؍‬ ؊0.02, P ‫؍‬ 0.4). Furthermore, we observed a positive correlation and association between daughter's TL and paternal lifespan (r ‫؍‬ 0.20, P < 0.001; ␤ ‫؍‬ 0.21, P ‫؍‬ 0.04), but not between daughter's TL and maternal lifespan (r ‫؍‬ ؊0.01, ␤ ‫؍‬ 0.04; both P ‫؍‬ not significant). Our data, which are based on one of the largest family studies of human TL, support a link between TL and aging and lifespan and suggest a strong genetic influence, possibly via an imprinting mechanism, on TL regulation.heritability ͉ parental effects ͉ sex specific ͉ imprinting ͉ Amish T elomeres are DNA capping structures that protect the ends of eukaryotic chromosomes. In vitro studies in mammalian cells suggest that telomere shortening triggers cellular senescence or apoptosis, depending on cell type (1-4). Studies in humans have shown that telomeres shorten with aging in various mitotic tissues and cell types (5-7). The rate of telomere attrition is slower in long-lived mammals compared with short-lived ones (8). Senescent cells accumulate with increasing age in vivo (9) and are thought to play an important role in organismal aging (10), which is characterized by physiologic and metabolic decline (4) and increasing susceptibility to several diseases associated with death (11). Thus, it is likely that telomere shortening may be mechanistically linked to organismal lifespan.Factors influencing telomere homeostasis are not fully known; however, it is likely that both environmental and biological factors play roles. Among the biological factors, a growing body of evidence suggests that genes play a very important role. Several genes that influence telomere length (TL) have been identified in model organisms (12, 13). In humans, shelterin, the protein complex that shapes and safeguards telomeres is made up of six subunits: TRF1, TRF2, TIN2, Rap1, TPP1, and POT1 (14). Other genes, such as TERT, UP1, Tankyrase, EST1, EST2, and EST3 are known to influence telomere homeostasis, and other genes such as YKU70, SIR4, and RIF2, encode proteins that bind specifically to the telomeres (13). In humans, the re...

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Cellular senescence and DNA repair

Cited by 65 publications

References 53 publications

DNA damage-induced cell death: lessons from the central nervous system

DNA damage-induced cell death: lessons from the central nervous system

ATM-like kinases and regulation of telomerase: lessons from yeast and mammals

Telomere length is paternally inherited and is associated with parental lifespan

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