Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction.
Bottom Line: Dispersion is promoted by the dissociation of Swi6/HP1 and cohesin Rad21 from telomeres, whereas disjunction occurs at anaphase after the phosphorylation of condensin subunit Cnd2.Strikingly, we demonstrate that deletion of Ccq1, a telomeric shelterin component, rescued cell death after Aurora inhibition by promoting the loading of condensin on chromosome arms.Our findings reveal an essential role for telomeres in chromosome arm segregation.
Affiliation: Laboratoire de biologie cellulaire et moléculaire du contrôle de la prolifération, Université de Toulouse, F-31062 Toulouse, France Centre National de la Recherche Scientifique, LBCMCP-UMR5088, F-31062 Toulouse, France.Show MeSH
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Mentions: To clarify the mechanisms leading to Aurora B–dependent telomere disjunction, we tested several key players in chromosome segregation. Recent studies in fission yeast have established that a condensin subunit (Cnd2) is an Aurora B substrate (Nakazawa et al., 2011; Tada et al., 2011). A condensin phosphomimetic mutant (cnd2-3E) alleviates the chromosome segregation defects in cells where Aurora B has been inactivated (Nakazawa et al., 2011; Tada et al., 2011). Hence, condensin may be the essential target of Aurora B at the fission yeast kinetochore. We speculated that phosphorylation of Cnd2 by Aurora B may also be sufficient to promote telomere dispersion or disjunction. To address this point, we used cnd2-3E ark1-as3 mutant cells that also expressed SPB (Cdc11-cfp), kinetochore (Ndc80-gfp and Mis6-rfp), and telomere (Taz1-gfp) markers. We scored the number of Taz1 foci relative to spindle length in wild-type or cnd2-3E cells after Aurora inhibition (Fig. 6 A, red dots). We found that the cnd2-3E mutant partially bypassed the telomere nondisjunction effects imposed by Aurora inhibition (Fig. 6, A and B; and Fig. S5 D) and was also able to rescue nucleolar segregation in 75.6 ± 3.2% (n = 97) of cells observed (Fig. S2 B).
Affiliation: Laboratoire de biologie cellulaire et moléculaire du contrôle de la prolifération, Université de Toulouse, F-31062 Toulouse, France Centre National de la Recherche Scientifique, LBCMCP-UMR5088, F-31062 Toulouse, France.