A Uve1p-Mediated Mismatch Repair Pathway in Schizosaccharomyces pombe

Abstract

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.

ACKNOWLEDGMENTS

We thank Angela Avery, Yoke Wah Kow, and Gerald Shadel for helpful discussions.

This work was supported by NIH grants CA73041 (P.W.D.), CA72647 (G.A.F.), and ES07940 (G.A.F. and S.D.) and by Medical Research Council of Canada grant MT-14352 (S.D.) S.D. is a Cancer Care Ontario Scientist. J.L.A.F. is a Queen’s University R. S. McLaughlin Fellow.