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Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts
Joint Authors
Watanabe, Masami
Yamashita, Shunichi
Suzuki, Keiji
Suzuki, Masatoshi
Kodama, Seiji
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-09-18
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Foci of phosphorylated histone H2AX and ATM are the surrogate markers of DNA double strand breaks.
We previously reported that the residual foci increased their size after irradiation, which amplifies DNA damage signals.
Here, we addressed whether amplification of DNA damage signal is involved in replicative senescence of normal human diploid fibroblasts.
Large phosphorylated H2AX foci (>1.5 μm diameter) were specifically detected in presenescent cells.
The frequency of cells with large foci was well correlated with that of cells positive for senescence-associated β-galactosidase staining.
Hypoxic cell culture condition extended replicative life span of normal human fibroblast, and we found that the formation of large foci delayed in those cells.
Our immuno-FISH analysis revealed that large foci partially localized at telomeres in senescent cells.
Importantly, large foci of phosphorylated H2AX were always colocalized with phosphorylated ATM foci.
Furthermore, Ser15-phosphorylated p53 showed colocalization with the large foci.
Since the treatment of senescent cells with phosphoinositide 3-kinase inhibitor, wortmannin, suppressed p53 phosphorylation, it is suggested that amplification of DNA damage signaling sustains persistent activation of ATM-p53 pathway, which is essential for replicative senescence.
American Psychological Association (APA)
Suzuki, Masatoshi& Suzuki, Keiji& Kodama, Seiji& Yamashita, Shunichi& Watanabe, Masami. 2012. Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts. Oxidative Medicine and Cellular Longevity،Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-462460
Modern Language Association (MLA)
Suzuki, Masatoshi…[et al.]. Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts. Oxidative Medicine and Cellular Longevity No. 2012 (2012), pp.1-8.
https://search.emarefa.net/detail/BIM-462460
American Medical Association (AMA)
Suzuki, Masatoshi& Suzuki, Keiji& Kodama, Seiji& Yamashita, Shunichi& Watanabe, Masami. Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts. Oxidative Medicine and Cellular Longevity. 2012. Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-462460
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-462460