title: Targeted deletion of mouse Rad1 leads to deficient cellular DNA damage responses.
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.
authors.affiliation: National Laboratory of Biomacromolecules, and the Center for Computational and Systems Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Zhang
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhishang
authors.initials: Z
authors.lastname: Hu
authors.forename: Lili
authors.initials: L
authors.lastname: An
authors.forename: Yikun
authors.initials: Y
authors.lastname: He
authors.forename: Haiying
authors.initials: H
authors.lastname: Hang
mesh_terms: D000818:Animals; D002455:Cell Division; D049109:Cell Proliferation; D004249:DNA Damage; D004260:DNA Repair; D053595:Embryonic Stem Cells / Q000378:metabolism; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016195:G2 Phase; D005720:Gamma Rays; D017353:Gene Deletion; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D014466:Ultraviolet Rays
chemical_list: D005092:Exonucleases; C559924:Rad1 protein, mouse; D006918:Hydroxyurea