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. 2011 Jun 2;2(5):410–422. doi: 10.1007/s13238-011-1049-7

Targeted deletion of mouse Rad1 leads to deficient cellular DNA damage responses

Chunbo Zhang 1,2, Yuheng Liu 1,3, Zhishang Hu 1, Lili An 1, Yikun He 2, Haiying Hang 1,✉
PMCID: PMC4875338  PMID: 21637962

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 G2/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 G2/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 G2/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.

Keywords: Rad1, DNA damage, checkpoint signaling, DNA repair, homologous recombination repair

Footnotes

These authors contributed equally to the work.

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