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Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction.

Reyes C, Serrurier C, Gauthier T, Gachet Y, Tournier S - J. Cell Biol. (2015)

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.

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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.

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Aurora B–dependent phosphorylation of condensin bypasses telomere nondisjunction but not dispersion. (A) Wild-type or the phosphomimetic mutant cnd2-3E cells were filmed through mitosis in the presence (Aurora inhibition, red, n = 48 control; n = 110 cnd2-3E) or absence (control, black, n = 42 control; n = 92 cnd2-3E) of 10 µM Napp1 and the number of Taz1 dots was counted according to spindle length. The data shown are from a single representative experiment out of three repeats. (B) Example of phenotypes seen in cnd2-3E ark1-as3 or cnd2-3A ark1-as3 cells treated or not with 10 µM Napp1. (C) Example of a wild-type cell control and a cnd2-3E ark1-as3 with Napp1 during mitotic progression. (D) The number of Taz1 foci (color code shown on the right) according to spindle length is analyzed from the movies shown in C. Note that in control cells (circles), telomere dispersion occurs before anaphase as opposed to cnd2-3E cells (squares) in the presence of Aurora inhibitor. Multiple cells were analyzed and display defects in telomere dispersion.
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fig6: Aurora B–dependent phosphorylation of condensin bypasses telomere nondisjunction but not dispersion. (A) Wild-type or the phosphomimetic mutant cnd2-3E cells were filmed through mitosis in the presence (Aurora inhibition, red, n = 48 control; n = 110 cnd2-3E) or absence (control, black, n = 42 control; n = 92 cnd2-3E) of 10 µM Napp1 and the number of Taz1 dots was counted according to spindle length. The data shown are from a single representative experiment out of three repeats. (B) Example of phenotypes seen in cnd2-3E ark1-as3 or cnd2-3A ark1-as3 cells treated or not with 10 µM Napp1. (C) Example of a wild-type cell control and a cnd2-3E ark1-as3 with Napp1 during mitotic progression. (D) The number of Taz1 foci (color code shown on the right) according to spindle length is analyzed from the movies shown in C. Note that in control cells (circles), telomere dispersion occurs before anaphase as opposed to cnd2-3E cells (squares) in the presence of Aurora inhibitor. Multiple cells were analyzed and display defects in telomere dispersion.

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).


Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction.

Reyes C, Serrurier C, Gauthier T, Gachet Y, Tournier S - J. Cell Biol. (2015)

Aurora B–dependent phosphorylation of condensin bypasses telomere nondisjunction but not dispersion. (A) Wild-type or the phosphomimetic mutant cnd2-3E cells were filmed through mitosis in the presence (Aurora inhibition, red, n = 48 control; n = 110 cnd2-3E) or absence (control, black, n = 42 control; n = 92 cnd2-3E) of 10 µM Napp1 and the number of Taz1 dots was counted according to spindle length. The data shown are from a single representative experiment out of three repeats. (B) Example of phenotypes seen in cnd2-3E ark1-as3 or cnd2-3A ark1-as3 cells treated or not with 10 µM Napp1. (C) Example of a wild-type cell control and a cnd2-3E ark1-as3 with Napp1 during mitotic progression. (D) The number of Taz1 foci (color code shown on the right) according to spindle length is analyzed from the movies shown in C. Note that in control cells (circles), telomere dispersion occurs before anaphase as opposed to cnd2-3E cells (squares) in the presence of Aurora inhibitor. Multiple cells were analyzed and display defects in telomere dispersion.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4362453&req=5

fig6: Aurora B–dependent phosphorylation of condensin bypasses telomere nondisjunction but not dispersion. (A) Wild-type or the phosphomimetic mutant cnd2-3E cells were filmed through mitosis in the presence (Aurora inhibition, red, n = 48 control; n = 110 cnd2-3E) or absence (control, black, n = 42 control; n = 92 cnd2-3E) of 10 µM Napp1 and the number of Taz1 dots was counted according to spindle length. The data shown are from a single representative experiment out of three repeats. (B) Example of phenotypes seen in cnd2-3E ark1-as3 or cnd2-3A ark1-as3 cells treated or not with 10 µM Napp1. (C) Example of a wild-type cell control and a cnd2-3E ark1-as3 with Napp1 during mitotic progression. (D) The number of Taz1 foci (color code shown on the right) according to spindle length is analyzed from the movies shown in C. Note that in control cells (circles), telomere dispersion occurs before anaphase as opposed to cnd2-3E cells (squares) in the presence of Aurora inhibitor. Multiple cells were analyzed and display defects in telomere dispersion.
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).

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.

View Article: PubMed Central - HTML - PubMed

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.

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Related in: MedlinePlus