Jcb_201409058 1..14

Telomeres maintain the integrity of linear chromosomes by preventing the unsolicited recruitment of DNA repair machineries to chromosome ends (de Lange, 2009; Dehé and Cooper, 2010; Jain and Cooper, 2010) and engaging telomerase to solve the end replication problem (Greider and Blackburn, 1985; Artandi and Cooper, 2009). At a distinct site on the chromosome, centromeres mediate the attachment of chromosomes to spindle microtubules in specific orientations that allow accurate chromosome segregation (Cheeseman and Desai, 2008; Watanabe, 2012). Despite these separate functions, telomeres and centromeres share several similarities. Both direct the assembly of specific nucleoprotein complexes and both, as a consequence of their underlying repetitive DNA sequences, are packaged into heterochromatin (Karpen and Allshire, 1997; Stimpson and Sullivan, 2010). Meiosis ensures the correct distribution of chromosomes from diploid progenitor cells to haploid gametes by incorporating two sequential nuclear divisions (meiosis I [MI] and II [MII]) after only a single round of DNA replication (Petronczki et al., 2003; Yanowitz, 2010). A widely conserved feature of meiotic prophase is formation of the telomere bouquet in which telomeres gather to a confined region of the nuclear membrane (NM), often near the centrosome (Chikashige et al., 1994; Chikashige et al., 1997; Scherthan, 2001). The bouquet stage is particularly well characterized in fission yeast. During mitotic interphase, telomeres localize to two or three clusters around the NM, whereas centromeres form a single cluster beneath the centrosome, which in fission yeast is called the spindle pole body (SPB) and is located on the cytoplasmic surface of the NM. This clustering requires interactions between centromeres and the SUN domain inner NM protein Sad1 (Hagan and Yanagida, 1995; Nabetani et al., 2001; Hou et al., 2012). Sad1 interacts with the outer NM KASH domain protein Kms1, which in turn contacts the SPB. Upon meiotic induction, the meiosis-specific proteins Bqt1 and Bqt2 interact with Rap1 (a partner of the telomeric dsDNA binding protein, Taz1) and recruit Sad1-Kms1 to the distally located telomeres (Chikashige et al., 2006). Kms1 interacts with cytoplasmic dynein, forming Telomeres and centromeres have traditionally been considered to perform distinct roles. During meiotic prophase, in a conserved chromosomal configuration called the bouquet, telomeres gather to the nuclear membrane (NM), often near centrosomes. We found previously that upon disruption of the fission yeast bouquet, centrosomes failed to insert into the NM at meiosis I and nucleate bipolar spindles. Hence, the trans-NM association of telomeres with centrosomes during prophase is crucial for efficient spindle formation. Nonetheless, in approximately half of bouquet-deficient meiocytes, spindles form properly. Here, we show that bouquet-deficient cells can successfully undergo meiosis using centromere–centrosome contact instead of telomere–centrosome contact to generate spindle formation. Accordingly, forced association between centromeres and centrosomes fully rescued the spindle defects incurred by bouquet disruption. Telomeres and centromeres both stimulate focal accumulation of the SUN domain protein Sad1 beneath the centrosome, suggesting a molecular underpinning for their shared spindlegenerating ability. Our observations demonstrate an unanticipated level of interchangeability between the two most prominent chromosomal landmarks. Telomeres and centromeres have interchangeable roles in promoting meiotic spindle formation