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Journal of Bacteriology, November 2000, p. 6036-6041, Vol. 182, No. 21
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mre11 and Rad50 from Pyrococcus furiosus: Cloning and Biochemical Characterization Reveal an Evolutionarily Conserved Multiprotein Machine

Karl-Peter Hopfner,1 Annette Karcher,1 David Shin,1 Cecilia Fairley,2 John A. Tainer,1 and James P. Carney3,*

Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 920371; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 947202; and Radiation Oncology Research Laboratory, Department of Radiation Oncology, and The Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 212013

Received 5 May 2000/Accepted 11 August 2000

The processing of DNA double-strand breaks is a critical event in nucleic acid metabolism. This is evidenced by the severity of phenotypes associated with deficiencies in this process in multiple organisms. The core component involved in double-strand break repair in eukaryotic cells is the Mre11-Rad50 protein complex, which includes a third protein, p95, in humans and Xrs2 in yeasts. Homologues of Mre11 and Rad50 have been identified in all kingdoms of life, while the Nbs1 protein family is found only in eukaryotes. In eukaryotes the Mre11-Rad50 complex has nuclease activity that is modulated by the addition of ATP. We have isolated the Mre11 and Rad50 homologues from the thermophilic archaeon Pyrococcus furiosus and demonstrate that the two proteins exist in a large, heat-stable complex that possesses single-strand endonuclease activity and ATP-dependent double-strand-specific exonuclease activity. These findings verify the identification of the P. furiosus Rad50 and Mre11 homologues and demonstrate that functional homologues with similar biochemical properties exist in all kingdoms of life.

* Corresponding author. Mailing address: Radiation Oncology Research Laboratory, University of Maryland School of Medicine, Bressler Research Building, 6-015, 655 West Baltimore St., Baltimore, MD 21201. Phone: (410) 706-4276. Fax: (410) 706-6138. E-mail: jcarney{at}som.umaryland.edu.

Journal of Bacteriology, November 2000, p. 6036-6041, Vol. 182, No. 21
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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