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 investigate whether telomere disjunction is subject to cell cycle regulation, we performed live imaging of cells endogenously expressing a nuclear envelope marker, Amo1-rfp (Pardo and Nurse, 2005), a spindle pole body (SPB) marker, Cdc11-cfp (Tournier et al., 2004), and a telomere marker protein, Taz1-gfp—a homologue of mammalian TRF1/TRF2 that binds exclusively to telomere repeats (Cooper et al., 1997; Vassetzky et al., 1999; Chikashige and Hiraoka, 2001; Fig. 1 A). Fission yeast has three chromosomes. During interphase, telomeres organized in one to three clusters in 96% of cells (n = 456; Fig. 1 A), but as cells progressed through mitosis, the number of Taz1 spots gradually increased to a maximum of 12 as a function of spindle length (Fig. 1 B). In early mitosis, the telomere clusters were still intact (Fig. 1 B, red diamonds), suggesting that cluster dispersion may occur at the metaphase-to-anaphase transition. To address this point, we followed individual taz1-gfp cdc11-cfp–expressing cells through mitosis. In early mitosis, also called phase 1 in fission yeast, a short spindle (up to 2.0 µm) is formed, as judged by SPB separation. In phase 2, this spindle length is maintained until sister chromatid separation (anaphase A). Phase 3 consists entirely of anaphase B, during which the spindle elongates along the long axis of the cell. We find that telomere cluster dispersion is initiated (from one to two foci) in phases 1 and 2, before anaphase A, and clusters fully dissociate during anaphase B (phase 3) when the chromosome arms are separated (telomere disjunction, from 6 to 12 foci; Fig. 1, C and D). An example of mitotic telomere dispersion and disjunction is shown in a single cell analysis (Fig. 1 C) together with a quantification of Taz1 foci during mitotic progression (Fig. 1 D).
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.