Targeted deletion of mouse Rad1 leads to deficient cellular DNA damage responses.
10.1007/s13238-011-1049-7
- Author:
Chunbo ZHANG
1
;
Yuheng LIU
;
Zhishang HU
;
Lili AN
;
Yikun HE
;
Haiying HANG
Author Information
1. National Laboratory of Biomacromolecules, and the Center for Computational and Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Division;
Cell Proliferation;
DNA Damage;
DNA Repair;
Embryonic Stem Cells;
metabolism;
Exonucleases;
genetics;
metabolism;
physiology;
G2 Phase;
Gamma Rays;
Gene Deletion;
Hydroxyurea;
pharmacology;
Mice;
Ultraviolet Rays
- From:
Protein & Cell
2011;2(5):410-422
- CountryChina
- Language:English
-
Abstract:
The Rad1 gene is evolutionarily conserved from yeast to human. The fission yeast Schizosaccharomyces pombe Rad1 ortholog promotes cell survival against DNA damage and is required for G(2)/M checkpoint activation. In this study, mouse embryonic stem (ES) cells with a targeted deletion of Mrad1, the mouse ortholog of this gene, were created to evaluate its function in mammalian cells. Mrad1 (-/-) ES cells were highly sensitive to ultraviolet-light (UV light), hydroxyurea (HU) and gamma rays, and were defective in G(2)/M as well as S/M checkpoints. These data indicate that Mrad1 is required for repairing DNA lesions induced by UV-light, HU and gamma rays, and for mediating G(2)/M and S/M checkpoint controls. We further demonstrated that Mrad1 plays an important role in homologous recombination repair (HRR) in ES cells, but a minor HRR role in differentiated mouse cells.
