Aurora A-dependent CENP-A phosphorylation at inner centromeres protects bioriented chromosomes against cohesion fatigue

Grégory Eot-Houllier (1) , Laura Magnaghi-Jaulin (1) , Geraldine Fulcrand (1) , Francois-Xavier Moyroud (1) , Solange Monier (1) , Christian Jaulin (1)

1 IGDR - Institut de Génétique et Développement de Rennes

Sustained spindle tension applied to sister centromeres during mitosis eventually leads to uncoordinated loss of sister chromatid cohesion, a phenomenon known as "cohesion fatigue." We report that Aurora A-dependent phosphorylation of serine 7 of the centromere histone variant CENP-A (p-CENP-AS7) protects bioriented chromosomes against cohesion fatigue. Expression of a non-phosphorylatable version of CENP-A (CENP-AS7A) weakens sister chromatid cohesion only when sister centromeres are under tension, providing the first evidence of a regulated mechanism involved in protection against passive cohesion loss. Consistent with this observation, p-CENP-AS7 is detected at the inner centromere where it forms a discrete domain. The depletion or inhibition of Aurora A phenocopies the expression of CENP-AS7A and we show that Aurora A is recruited to centromeres in a Bub1-dependent manner. We propose that Aurora A-dependent phosphorylation of CENP-A at the inner centromere protects chromosomes against tension-induced cohesion fatigue until the last kinetochore is attached to spindle microtubules.

Domains: Life Sciences [q-bio]; Genetics; Life Sciences [q-bio]; Life Sciences [q-bio]; Cellular Biology; Subcellular Processes [q-bio.SC]

Grégory Eot-Houllier, Laura Magnaghi-Jaulin, Geraldine Fulcrand, Francois-Xavier Moyroud, Solange Monier, et al.. Aurora A-dependent CENP-A phosphorylation at inner centromeres protects bioriented chromosomes against cohesion fatigue. Nature Communications, 2018, 9 (1), pp.1888. ⟨10.1038/s41467-018-04089-9⟩. ⟨hal-01863221⟩