Dataset Information

DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion.

ABSTRACT: DNA damage can induce a tumor suppressive response termed cellular senescence. Damaged senescent cells permanently arrest growth, secrete inflammatory cytokines and other proteins and harbor persistent nuclear foci that contain DNA damage response (DDR) proteins. To understand how persistent damage foci differ from transient foci that mark repairable DNA lesions, we identify sequential events that differentiate transient foci from persistent foci, which we term 'DNA segments with chromatin alterations reinforcing senescence' (DNA-SCARS). Unlike transient foci, DNA-SCARS associate with PML nuclear bodies, lack the DNA repair proteins RPA and RAD51, lack single-stranded DNA and DNA synthesis and accumulate activated forms of the DDR mediators CHK2 and p53. DNA-SCARS form independently of p53, pRB and several other checkpoint and repair proteins but require p53 and pRb to trigger the senescence growth arrest. Importantly, depletion of the DNA-SCARS-stabilizing component histone H2AX did not deplete 53BP1 from DNA-SCARS but diminished the presence of MDC1 and activated CHK2. Furthermore, depletion of H2AX reduced both the p53-dependent senescence growth arrest and p53-independent cytokine secretion. DNA-SCARS were also observed following severe damage to multiple human cell types and mouse tissues, suggesting that they can be used in combination with other markers to identify senescent cells. Thus, DNA-SCARS are dynamically formed distinct structures that functionally regulate multiple aspects of the senescent phenotype.

SUBMITTER: Rodier F

PROVIDER: S-EPMC3001408 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion.

Rodier Francis F Muñoz Denise P DP Teachenor Robert R Chu Victoria V Le Oanh O Bhaumik Dipa D Coppé Jean-Philippe JP Campeau Eric E Beauséjour Christian M CM Kim Sahn-Ho SH Davalos Albert R AR Campisi Judith J

Journal of cell science 20101130 Pt 1

DNA damage can induce a tumor suppressive response termed cellular senescence. Damaged senescent cells permanently arrest growth, secrete inflammatory cytokines and other proteins and harbor persistent nuclear foci that contain DNA damage response (DDR) proteins. To understand how persistent damage foci differ from transient foci that mark repairable DNA lesions, we identify sequential events that differentiate transient foci from persistent foci, which we term 'DNA segments with chromatin alter ...[more]

PMID: 21118958

Similar Datasets

Project description:Massage therapy is commonly used for the physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. While there is some evidence that massage may relieve pain in injured muscle, the cellular effects remain unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of eleven young, male participants after exercised-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline (rest), immediately after 10 minutes of massage treatment (0h), and after a 2.5 hour period of recovery. We found that massage activated the mechanotransduction signaling pathways FAK and Erk1/2, potentiated mitochondrial biogenesis signaling (nuclear PGC-1α), and mitigated the rise in NFkB (p65) nuclear accumulation caused by muscle trauma. Moreover, in spite of having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines TNF-α and IL-6 and reduced HSP27 phosphorylation, effectively mitigating cellular stress resulting from myofiber injury. In summary, massage therapy appears to be clinically beneficial when administered to acutely damaged skeletal muscle by reducing inflammation and promoting mitochondrial biogenesis. 55 muscle biopsies were used in this study as material to evaluate the effects of massage on gene expression. These biopsies were taken from the vastus lateralis of eleven healthy recreationally active males with full ethical approval at McMaster's university. Each individual had an initial biopsy at rest (baseline), followed by exercist testing for peak aerobic capacity. On a second visit, the individual performed a bout of exhaustive aerobic exercise, prior to recieving a randomized massage treatment to one leg. Immediatley following the exercise, subjects were allowed to recover for 10 minutes, while massage oil was lightly applied to both quadriceps. Then a single leg was randomized to recieve massage treatment for 10 minutes. Subjects then rested for 10 minutes, and one additional biopsies were carried out (on each leg). Two and half hours later (3 hours after the cessation of the exercise bout), 2 more biopsies were taken (one from each leg). This amounted to 5 biopsies from each individual.

Dataset Information

DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion.

Publications

DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure