Past studies demonstrate that amplification of DNA damage signal relates to persistent activation of ATMp53 process adequate for performing irreversible Dasatinib ic50 arrest in response to ionizing radiation. In fact, residual foci, which sustain for over many times following irradiation, are larger foci, which are essential for right activation of p53. Today’s study demonstrably demonstrated that formation of large foci also takes place in replicative senescent cells.. Our answers are the following: increase of cells with large foci is well correlated with the senescence induction, and hypoxic mobile culture, which runs replicative life span, delays the development of large foci, indicate good relationship between amplification of DNA damage signals and induction of replicative senescence. It has been thought that telomere dysfunction results in activation of DNA damage response. Dysfunctional telomere can be detected by foci development of DNA damage checkpoint facets which supported with telomere FISH Cellular differentiation sign, so-called telomere induced foci, and we also detected TIF in 25.5-inch of senescent cells.. It is broadly speaking thought that TIF represents uncapped telomere exposing telomeric DNA ends. Thus, it is assumed that unreparable DSBs causes continuous activation of DNA damage response. It has been shown that telomere telomere fusionmediated dicentric chromosomes were produced in senescent normal human fibroblasts of WI 38 and MRC 5, suggesting another possibility that TIF might be reflected the location on chromosome produced from mix. Our immuno FISH investigation certainly demonstrated that large foci without telomere FISH transmission in 75% of senescent cells. Nakamura et al. Exactly analyzed foci creation with metaphase chromosome spreads of presenescent WI 38 and BJ normal human fibroblasts. They found localization of foci at the conclusion of chromosome which met inhibitors lacked telomere FISH sign in over 508 of foci detected in presenescent metaphase spreads. Therefore, large foci creation without telomere FISH sign within our telomere FISH analysis may include such foci. Alternately, subsequent telomere telomere blend, Fusion Bridge Breakage pattern may trigger DSBs at interstitial chromatin region. Once dysfunctional telomeres are merged and produce dicentric chromosome, two centromeres are pulled in opposite instructions all through anaphase. This type of chromosome regionally gets a tension, sooner or later, DNA break is set up at interstitial chromatin place of dicentric chromosome. On the basis of the model, dysfunctional telomeres might be in the one system of large foci formation in replicative senescence, but interstitial chromatin region is also the candidate to provide DNA ends. Formationof large foci invokes ATM p53 process, which triggers p21 transactivation.