Journal
CELL DEATH AND DIFFERENTIATION
Volume 13, Issue 2, Pages 223-235Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401747
Keywords
DNA polymerase delta1; p53; flathead; zebrafish; replication; apoptosis; S-phase checkpoint
Categories
Funding
- NIGMS NIH HHS [R01 GM063904-01, R01 GM063904] Funding Source: Medline
Ask authors/readers for more resources
Cell culture work has identified the tumor suppressor p53 as a component of the S-phase checkpoint control system, while in vivo studies of this role of p53 in whole-vertebrate systems were limited. Here, we describe zebrafish mutants in the DNA polymerase delta catalytic subunit 1, based on the positional cloning of the flathead (fla) gene. fla mutants display specific defects in late proliferative zones, such as eyes, brain and cartilaginous elements of the visceral head skeleton, where cells display compromised DNA replication, followed by apoptosis, and partial or complete loss of affected tissues. Antisense-mediated knockdown of p53 in fla mutants leads to a striking rescue of all phenotypic traits, including completion of replication, survival of cells, and normal differentiation and tissue formation. This indicates that under replication-compromised conditions, the p53 branch of the S-phase checkpoint is responsible for eliminating stalled cells that, given more time, would have otherwise finished their normal developmental program.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available