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Molecular and Cellular Biology, July 1999, p. 4703-4710, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Uve1p-Mediated Mismatch Repair Pathway in Schizosaccharomyces pombe

Balveen Kaur,1,2 J. Lee A. Fraser,3 Greg A. Freyer,4 Scott Davey,3,5 and Paul W. Doetsch1,6,*

Department of Biochemistry1 and Division of Biological and Biomedical Sciences,2 Graduate Program in Biochemistry and Cell and Developmental Biology, and Division of Cancer Biology, Department of Radiation Oncology,6 Emory University, School of Medicine, Atlanta, Georgia 30322; Department of Pathology3 and Departments of Oncology and Biochemistry,5 Queen's University, Kingston, Ontario K7L 3N6, Canada; and Department of Environmental Health Sciences, School of Public Health, and Department of Anatomy and Cell Biology, Columbia University, New York, New York 100324

Received 11 January 1999/Returned for modification 10 March 1999/Accepted 8 April 1999

UV damage endonuclease (Uve1p) from Schizosaccharomyces pombe was initially described as a DNA repair enzyme specific for the repair of UV light-induced photoproducts and proposed as the initial step in an alternative excision repair pathway. Here we present biochemical and genetic evidence demonstrating that Uve1p is also a mismatch repair endonuclease which recognizes and cleaves DNA 5' to the mispaired base in a strand-specific manner. The biochemical properties of the Uve1p-mediated mismatch endonuclease activity are similar to those of the Uve1p-mediated UV photoproduct endonuclease. Mutants lacking Uve1p display a spontaneous mutator phenotype, further confirming the notion that Uve1p plays a role in mismatch repair. These results suggest that Uve1p has a surprisingly broad substrate specificity and may function as a general type of DNA repair protein with the capacity to initiate mismatch repair in certain organisms.

* Corresponding author. Mailing address: Department of Biochemistry, 4123 Rollins Research Center, Emory University, School of Medicine, Atlanta, GA 30322. Phone: (404) 727-0409. Fax: (404) 727-3954. E-mail: medpwd{at}emory.edu.

Molecular and Cellular Biology, July 1999, p. 4703-4710, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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