Jcb_201405028 1..11

Condensin is a DNA compaction machine that functions in chromosome architecture, nucleolar organization, and chromo­ some segregation (Hirano, 2006). Condensin can introduce su­ percoils and decatenate topologically linked circles. The most prominent sites of condensin localization in the nucleus are the nucleolus, pericentric chromatin, and central axis of condensed metaphase chromosomes. Condensin is also essential for mech­ anisms of force balance between the pericentromere hetero­ chromatin and spindle microtubules in metaphase (Stephens et al., 2011, 2013a). Condensin interacts with several key tran­ scription factors, including RNA polymerase III transcription factors (TFIIIC and TFIIIB; Haeusler et al., 2008). This inter­ action is responsible for the enrichment of tRNA genes to the nucleolar periphery observed in budding yeast. Recently, it has been shown that the monopolin complex recruits condensin to the pericentromere (Brito et al., 2010; Burrack et al., 2013). The monopolin complex is sequestered in the nucleolus until the onset of anaphase, in which it migrates to the kinetochore (Brito et al., 2010; Burrack et al., 2013). In meiosis, monopolin is thought to cross­link sister kinetochores to ensure that sister chromatids segregate to the same pole. None of the known mechanisms attributed to condensin indicate how it functions in force balance in metaphase. Budding yeast lacks canonical pericentric heterochroma­ tin observed in most organisms. Centromeres in Saccharomyces cerevisiae are specified in a site­specific manner (point centro­ mere) but share several features of the surrounding pericentric chromatin characteristic of that found in multicellular organ­ isms. Condensin and cohesin are enriched 3× in the 30–50­kb region surrounding the point centromere (Blat and Kleckner, 1999; Megee et al., 1999; D’Ambrosio et al., 2008). tRNA genes, found in the pericentric regions of many organisms (Kuhn et al., 1991; Iwasaki and Noma, 2012), are enriched 1.8× in the peri­ centromere of budding yeast (32/307 tRNA genes in the 50 kb surrounding the CEN [centromere] sequence in the 16 chromo­ somes). tRNAs are modified by several factors, including dys­ kerin. Dyskerin binds to and stabilizes small noncoding RNAs, which together with other components (H/ACA small nucleolar RNP [snoRNP]) catalyzes the conversion of uridine to pseudou­ ridine in nascent ribosomal RNA and tRNA (Hoang and Ferré­ D’Amaré, 2001). Dyskerin is a component of telomerase and is required for telomere maintenance in humans (Gu et al., 2009; Gardano et al., 2012). Dyskerin has been localized to the Condensin is enriched in the pericentromere of budding yeast chromosomes where it is constrained to the spindle axis in metaphase. Pericentric condensin contributes to chromatin compaction, resistance to microtubule-based spindle forces, and spindle length and variance regulation. Condensin is clustered along the spindle axis in a heterogeneous fashion. We demonstrate that pericentric enrichment of condensin is mediated by interactions with transfer ribonucleic acid (tRNA) genes and their regulatory factors. This recruitment is important for generating axial tension on the pericentromere and coordinating movement between pericentromeres from different chromosomes. The interaction between condensin and tRNA genes in the pericentromere reveals a feature of yeast centromeres that has profound implications for the function and evolution of mitotic segregation mechanisms. Dyskerin, tRNA genes, and condensin tether pericentric chromatin to the spindle axis in mitosis