DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development.
During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration,...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2809090?pdf=render |
| _version_ | 1818958771812040704 |
|---|---|
| author | Yosuke Ichijima Ken-ichi Yoshioka Yoshiko Yoshioka Keitaro Shinohe Hiroaki Fujimori Junya Unno Masatoshi Takagi Hidemasa Goto Masaki Inagaki Shuki Mizutani Hirobumi Teraoka |
| author_facet | Yosuke Ichijima Ken-ichi Yoshioka Yoshiko Yoshioka Keitaro Shinohe Hiroaki Fujimori Junya Unno Masatoshi Takagi Hidemasa Goto Masaki Inagaki Shuki Mizutani Hirobumi Teraoka |
| author_sort | Yosuke Ichijima |
| collection | DOAJ |
| description | During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress. |
| first_indexed | 2024-12-20T11:31:03Z |
| format | Article |
| id | doaj.art-1487fcda76eb4ba6b3ea1778ac53e194 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T11:31:03Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1487fcda76eb4ba6b3ea1778ac53e1942022-12-21T19:42:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0151e882110.1371/journal.pone.0008821DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development.Yosuke IchijimaKen-ichi YoshiokaYoshiko YoshiokaKeitaro ShinoheHiroaki FujimoriJunya UnnoMasatoshi TakagiHidemasa GotoMasaki InagakiShuki MizutaniHirobumi TeraokaDuring tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress.http://europepmc.org/articles/PMC2809090?pdf=render |
| spellingShingle | Yosuke Ichijima Ken-ichi Yoshioka Yoshiko Yoshioka Keitaro Shinohe Hiroaki Fujimori Junya Unno Masatoshi Takagi Hidemasa Goto Masaki Inagaki Shuki Mizutani Hirobumi Teraoka DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development. PLoS ONE |
| title | DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development. |
| title_full | DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development. |
| title_fullStr | DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development. |
| title_full_unstemmed | DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development. |
| title_short | DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development. |
| title_sort | dna lesions induced by replication stress trigger mitotic aberration and tetraploidy development |
| url | http://europepmc.org/articles/PMC2809090?pdf=render |
| work_keys_str_mv | AT yosukeichijima dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT kenichiyoshioka dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT yoshikoyoshioka dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT keitaroshinohe dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT hiroakifujimori dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT junyaunno dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT masatoshitakagi dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT hidemasagoto dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT masakiinagaki dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT shukimizutani dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment AT hirobumiteraoka dnalesionsinducedbyreplicationstresstriggermitoticaberrationandtetraploidydevelopment |