| RRC ID |
4110
|
| 著者 |
Yamaguchi M, Fujimori-Tonou N, Yoshimura Y, Kishi T, Okamoto H, Masai I.
|
| タイトル |
Mutation of DNA primase causes extensive apoptosis of retinal neurons through the activation of DNA damage checkpoint and tumor suppressor p53.
|
| ジャーナル |
Development
|
| Abstract |
Apoptosis is often observed in developing tissues. However, it remains unclear how the apoptotic pathway is regulated during development. To clarify this issue, we isolated zebrafish mutants that show extensive apoptosis of retinal cells during their development. pinball eye (piy) is one such mutant, in which retinal stem cells proliferate normally but almost all retinal neurons undergo apoptosis during differentiation. We found that a missense mutation occurred in the small subunit of DNA primase (Prim1) in the piy mutant. DNA primase is essential for DNA replication; however, this mutation does not affect cell proliferation but rather induces neuronal apoptosis. RNA synthesis catalyzed by Prim1 is important for the activation of the DNA damage response, which may activate Ataxia telangiectasia mutated (ATM), Checkpoint kinase 2 (Chk2) and the tumor suppressor p53. We found that the apoptosis induced by the prim1 mutation depends on the ATM-Chk2-p53 apoptotic pathway. These data suggest that the surveillance system of genome integrity strongly influences the cell fate decision between differentiation and apoptosis during retinal neurogenesis in zebrafish.
|
| 巻・号 |
135(7)
|
| ページ |
1247-57
|
| 公開日 |
2008-4-1
|
| DOI |
10.1242/dev.011015
|
| PII |
dev.011015
|
| PMID |
18287205
|
| MeSH |
Animals
Animals, Genetically Modified
Apoptosis*
Checkpoint Kinase 2
DNA Damage
DNA Primase / genetics*
Embryo, Nonmammalian
Enzyme Activation / genetics
Models, Biological
Mutation, Missense*
Neurons / pathology
Protein Serine-Threonine Kinases / metabolism*
Retina / cytology
Tumor Suppressor Protein p53 / metabolism*
Zebrafish / embryology
Zebrafish / genetics
|
| IF |
5.611
|
| 引用数 |
22
|
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
|
| リソース情報 |
| ゼブラフィッシュ |
RIKEN WT (RW)
rw021 (Tg(ath5:GFP))?
rw255(piy)? |
