@article{5eda0d586729403482a18f70e0732169,
title = "A quantitative analysis of cohesin decay in mitotic fidelity",
abstract = "Sister chromatid cohesion mediated by cohesin is essential for mitotic fidelity. It counteracts spindle forces to prevent premature chromatid individualization and random genome segregation. However, it is unclear what effects a partial decline of cohesin may have on chromosome organization. In this study, we provide a quantitative analysis of cohesin decay by inducing acute removal of defined amounts of cohesin from metaphase-arrested chromosomes. We demonstrate that sister chromatid cohesion is very resistant to cohesin loss as chromatid disjunction is only observed when chromosomes lose >80% of bound cohesin. Removal close to this threshold leads to chromosomes that are still cohered but display compromised chromosome alignment and unstable spindle attachments. Partial cohesin decay leads to increased duration of mitosis and susceptibility to errors in chromosome segregation. We propose that high cohesin density ensures centromeric chromatin rigidity necessary to maintain a force balance with the mitotic spindle. Partial cohesin loss may lead to chromosome segregation errors even when sister chromatid cohesion is fulfilled.",
author = "Sara Carvalhal and Alexandra Tavares and Santos, {Mariana B.} and Mihailo Mirkovic and Oliveira, {Raquel A.}",
note = "Funding Information: This work was supported by the following grants awarded to R.A. Oliveira: Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia Investigator grant (IF/00851/2012/CP0185/CT0004), European Molecular Biology Organization Installation Grant (IG2778), and European Research Council Starting Grant (ERC-2014-STG-638917). The authors declare no competing financial interests. Funding Information: We thank S. Heidmann, R. Karess, C. Lehner, and P. O{\textquoteright}Farrell for fly strains, antibodies, and plasmids, Nina Roothans (Instituto Superior Tecnico summer student) for the help with imaging analysis, and all the members of the R.A. Oliveira laboratory for discussions and comments. We thank the technical support of Instituto Gulbenkian de Ciencia{\textquoteright}s Advanced Imaging Facility, supported by national Portuguese funding (PPBI-POCI-01-0145-FEDER-022122), and the Fly Facility, supported by Congento (LISBOA-01-0145-FEDER-022170). These two programs are cofinanced by Lisboa Regional Operational Program (Lisboa 2020) under the Portugal 2020 Partnership Agreement through the European Regional Development Fund (FEDER) and Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (FCT; Portugal). Publisher Copyright: {\textcopyright} 2018 Carvalhal et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).",
year = "2018",
month = oct,
day = "1",
doi = "10.1083/JCB.201801111",
language = "English",
volume = "217",
pages = "3343--3353",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "10",
}