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
Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [47 references]  Display  Hide  Download
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01863221
Contributor : Laurent Jonchère <>
Submitted on : Thursday, July 18, 2019 - 10:43:39 AM
Last modification on : Friday, July 19, 2019 - 8:24:57 AM

File

s41467-018-04089-9.pdf
Publisher files allowed on an open archive

Identifiers

Collections

UNIV-RENNES | UR1-UFR-SVE | BIOSIT | IGDR | UNIV-RENNES1

Citation

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, Nature Publishing Group, 2018, 9 (1), pp.1888. ⟨10.1038/s41467-018-04089-9⟩. ⟨hal-01863221⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Record views

31

Files downloads

16