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A more recent version of this article appeared on January 1, 2004
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Submitted on August 13, 2003
Revised on September 5, 2003
Accepted on September 6, 2003
1 Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037
2 Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037
3 Department of Molecular Biology, Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037
* Corresponding author. E-mail address: prussell{at}scripps.edu.
In most eukaryotes, genes encoding ribosomal RNAs (rDNA) are clustered in long tandem head-to-tail repeats. Studies of S. cerevisiae have indicated that rDNA copy number is maintained through recombination events associated with site-specific blockage of replication forks (RF). Here we describe two Schizosaccharomyces pombe proteins, homologues of S. cerevisiae Slx1 and Slx4, as subunits of a novel type of endonuclease that maintains rDNA copy number. The Slx1-Slx4 dependent endonuclease introduces single-strand cuts in duplex DNA on the 3' side of junctions with single-strand DNA. Deletion of Slx1 or Rqh1 RecQ-like DNA helicase provokes rDNA contraction, while simultaneous elimination of Slx1-Slx4 endonuclease and Rqh1 is lethal. Slx1 associates with chromatin at two foci characteristic of the two rDNA repeat loci in Schizosaccharomyces pombe. We propose a model in which the Slx1-Slx4 complex is involved in the control of the expansion and contraction of the rDNA loci by initiating recombination events at stalled RFs.
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