DOI: 10.1073/pnas.96.13.7376. Disruption of <i>mRad50</i> causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation

Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation

10.1073/pnas.96.13.7376

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The Mre11/Rad50 protein complex functions in diverse aspects of the cellular response to double-strand breaks (DSBs), including the detection of DNA damage, the activation of cell cycle checkpoints, and DSB repair. Whereas genetic analyses in Saccharomyces cerevisiae have provided insight regarding DSB repair functions of this highly conserved complex, the implication of the human complex in Nijmegen breakage syndrome reveals its role in cell cycle checkpoint functions. We established mRad50 mutant mice to examine the role of the mammalian Mre11/Rad50 protein complex in the DNA damage response. Early embryonic cells deficient in mRad50 are hypersensitive to ionizing radiation, consistent with a role for this complex in the repair of ionizing radiation-induced DSBs. However, the null mrad50 mutation is lethal in cultured embryonic stem cells and in early developing embryos, indicating that the mammalian Mre11/Rad50 protein complex mediates functions in normally growing cells that are essential for viability.

Bibliography

Luo, G., Yao, M. S., Bender, C. F., Mills, M., Bladl, A. R., Bradley, A., & Petrini, J. H. J. (1999). Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation. Proceedings of the National Academy of Sciences, 96(13), 7376â7381.

Authors 7

Guangbin Luo (first)
Michelle S. Yao (additional)
Carla F. Bender (additional)
Michael Mills (additional)
Anthony R. Bladl (additional)
Allan Bradley (additional)
John H. J. Petrini (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:32 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:28 p.m.)
Indexed	5 days, 1 hour ago (Aug. 27, 2025, 11:47 a.m.)
Issued	26 years, 2 months ago (June 22, 1999)
Published	26 years, 2 months ago (June 22, 1999)
Published Online	26 years, 2 months ago (June 22, 1999)
Published Print	26 years, 2 months ago (June 22, 1999)

Funders 0

None

BibTeX

@article{Luo_1999, title={Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.13.7376}, DOI={10.1073/pnas.96.13.7376}, number={13}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Luo, Guangbin and Yao, Michelle S. and Bender, Carla F. and Mills, Michael and Bladl, Anthony R. and Bradley, Allan and Petrini, John H. J.}, year={1999}, month=jun, pages={7376–7381} }

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