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| Content Provider | PubMed Central |
|---|---|
| Author | Atsumi, Yuko Fujimori, Hiroaki Fukuda, Hirokazu Aki, Inase Shinohe, Keitaro Yoshioka, Yoshiko Mima, Shikanai Ichijima, Yosuke Unno, Junya Mizutani, Shuki Tsuchiya, Naoto Hippo, Yoshitaka Hitoshi, Nakagama Masutani, Mitsuko Teraoka, Hirobumi Yoshioka, Ken-ichi |
| Editor | Michael, Polymenis |
| Copyright Year | 2011 |
| Abstract | Normal cells, both in vivo and in vitro, become quiescent after serial cell proliferation. During this process, cells can develop immortality with genomic instability, although the mechanisms by which this is regulated are unclear. Here, we show that a growth-arrested cellular status is produced by the down-regulation of histone H2AX in normal cells. Normal mouse embryonic fibroblast cells preserve an H2AX diminished quiescent status through p53 regulation and stable-diploidy maintenance. However, such quiescence is abrogated under continuous growth stimulation, inducing DNA replication stress. Because DNA replication stress-associated lesions are cryptogenic and capable of mediating chromosome-bridge formation and cytokinesis failure, this results in tetraploidization. Arf/p53 module-mutation is induced during tetraploidization with the resulting H2AX recovery and immortality acquisition. Thus, although cellular homeostasis is preserved under quiescence with stable diploidy, tetraploidization induced under growth stimulation disrupts the homeostasis and triggers immortality acquisition. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0023432 |
| Starting Page | 23432 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 8 |
| Volume Number | 6 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2011-08-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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