Regulation of Telomere Structure and Functions by Subunits of the INO80 Chromatin Remodeling Complex

Abstract

ATP-dependent chromatin remodeling complexes have been implicated in the regulation of transcription, replication, and more recently DNA double-strand break repair. Here we report that the Ies3p subunit of the Saccharomyces cerevisiae INO80 chromatin remodeling complex interacts with a conserved tetratricopeptide repeat domain of the telomerase protein Est1p. Deletion of IES3 and some other subunits of the complex induced telomere elongation and altered telomere position effect. In telomerase-negative mutants, loss of Ies3p delayed the emergence of recombinational survivors and stimulated the formation of extrachromosomal telomeric circles in survivors. Deletion of IES3 also resulted in heightened levels of telomere-telomere fusions in telomerase-deficient strains. In addition, a delay in survivor formation was observed in an Arp8p-deficient mutant. Because Arp8p is required for the chromatin remodeling activity of the INO80 complex, the complex may promote recombinational telomere maintenance by altering chromatin structure. Consistent with this notion, we observed preferential localization of multiple subunits of the INO80 complex to telomeres. Our results reveal novel functions for a subunit of the telomerase complex and the INO80 chromatin remodeling complex.

SUPPLEMENTAL MATERIAL

We thank Stephan Mercand, Brad Cairnes, and Ginger Zakian for yeast strains and/or advice and members of our labs for comments on the manuscript.

This work was supported by NIH GM62631 and the Irma T. Hirschl/Monique Weill-Caulier Research Award to N.F.L.; NCI 1K22CA100017, ACS RSG-05-060-01-GMC, and NIEHS ES07784 to X.S.; and the M. D. Anderson Odyssey Fellowship and Theodore N. Law Award to A.J.M. The Department of Microbiology and Immunology at Weill Cornell Medical College gratefully acknowledges the support of the William Randolph Hearst Foundation.