{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:56:46Z","timestamp":1768471006182,"version":"3.49.0"},"posted":{"date-parts":[[2018,2,8]]},"group-title":"Cell Biology","reference-count":51,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2018,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Sister chromatid cohesion is essential for faithful mitosis, as premature cohesion loss leads to random chromosome segregation and aneuploidy, resulting in abnormal development. To identify specific conditions capable of restoring defects associated with cohesion loss, we screened for genes whose depletion modulates\n                  <jats:italic>Drosophila<\/jats:italic>\n                  wing development when sister chromatid cohesion is impaired. Cohesion deficiency was induced by knock-down of the acetyltransferase Separation anxiety (San)\/Naa50, a cohesin complex stabilizer. Several genes whose function impacts wing development upon cohesion loss were identified. Surprisingly, knockdown of key Spindle Assembly Checkpoint (SAC) proteins, Mad2 and Mps1, suppressed developmental defects associated with San depletion. SAC impairment upon cohesin removal, triggered by San depletion or artificial removal of the cohesin complex, prevented extensive genome shuffling, reduced segregation defects and restored cell survival. This counterintuitive phenotypic suppression was caused by an intrinsic bias for efficient chromosome bi-orientation at mitotic entry, coupled with slow engagement of error-correction reactions. We conclude that mitotic timing determines the severity of defects associated with cohesion deficiency. Therefore, although divisions are still error-prone, SAC inactivation enhances cell survival and tissue homeostasis upon cohesion loss.\n                <\/jats:p>","DOI":"10.1101\/262204","type":"posted-content","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T11:06:32Z","timestamp":1518433592000},"source":"Crossref","is-referenced-by-count":0,"title":["Absence of the Spindle Assembly Checkpoint restores mitotic fidelity upon loss of sister chromatid cohesion"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-8599","authenticated-orcid":false,"given":"Rui D.","family":"Silva","sequence":"first","affiliation":[]},{"given":"Mihailo","family":"Mirkovic","sequence":"additional","affiliation":[]},{"given":"Leonardo G.","family":"Guilgur","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-557X","authenticated-orcid":false,"given":"Om S.","family":"Rathore","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1641-3403","authenticated-orcid":false,"given":"Rui Gon\u00e7alo","family":"Martinho","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8293-8603","authenticated-orcid":false,"given":"Raquel A.","family":"Oliveira","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2019071819065895000_262204v2.1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E12-02-0117"},{"key":"2019071819065895000_262204v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.05.039"},{"key":"2019071819065895000_262204v2.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1201538"},{"key":"2019071819065895000_262204v2.4","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1242\/dev.118.2.401","article-title":"Targeted gene expression as a means of altering cell fates and generating dominant phenotypes","volume":"118","year":"1993","journal-title":"Development"},{"key":"2019071819065895000_262204v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1570"},{"key":"2019071819065895000_262204v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/22133"},{"key":"2019071819065895000_262204v2.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt882"},{"key":"2019071819065895000_262204v2.8","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.105.046441"},{"key":"2019071819065895000_262204v2.9","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.cub.2011.05.032","article-title":"Cohesion fatigue induces chromatid separation in cells delayed at metaphase","volume":"21","year":"2011","journal-title":"Current biology : CB"},{"key":"2019071819065895000_262204v2.10","doi-asserted-by":"crossref","first-page":"8399","DOI":"10.1038\/ncomms9399","article-title":"Defective sister chromatid cohesion is synthetically lethal with impaired APC\/C function","volume":"6","year":"2015","journal-title":"Nature communications"},{"key":"2019071819065895000_262204v2.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206675109"},{"key":"2019071819065895000_262204v2.12","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3494"},{"key":"2019071819065895000_262204v2.13","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.cub.2005.12.040","article-title":"Condensin I Stabilizes Chromosomes Mechanically through a Dynamic Interaction in Live Cells","volume":"16","year":"2006","journal-title":"Current biology : CB"},{"key":"2019071819065895000_262204v2.14","doi-asserted-by":"crossref","first-page":"8894","DOI":"10.1038\/ncomms9894","article-title":"Aneuploidy causes premature differentiation of neural and intestinal stem cells","volume":"6","year":"2015","journal-title":"Nature communications"},{"key":"2019071819065895000_262204v2.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)80008-8"},{"key":"2019071819065895000_262204v2.16","doi-asserted-by":"publisher","DOI":"10.1038\/nature07098"},{"key":"2019071819065895000_262204v2.17","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200701043"},{"key":"2019071819065895000_262204v2.18","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3153"},{"key":"2019071819065895000_262204v2.19","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1010-919"},{"key":"2019071819065895000_262204v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.12.018"},{"key":"2019071819065895000_262204v2.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404102101"},{"key":"2019071819065895000_262204v2.22","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061611-090435"},{"key":"2019071819065895000_262204v2.23","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200407090"},{"key":"2019071819065895000_262204v2.24","doi-asserted-by":"crossref","unstructured":"Mariezcurrena, A. , and F. Uhlmann . 2017. Observation of DNA intertwining along authentic budding yeast chromosomes. Genes Dev.","DOI":"10.1101\/gad.305557.117"},{"key":"2019071819065895000_262204v2.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)80007-6"},{"key":"2019071819065895000_262204v2.26","first-page":"470","article-title":"Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback","volume":"13","year":"2015","journal-title":"Cell reports"},{"key":"2019071819065895000_262204v2.27","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-58592-5_20"},{"key":"2019071819065895000_262204v2.28","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2163"},{"key":"2019071819065895000_262204v2.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.09.007"},{"key":"2019071819065895000_262204v2.30","doi-asserted-by":"publisher","DOI":"10.1038\/381316a0"},{"key":"2019071819065895000_262204v2.31","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2018"},{"key":"2019071819065895000_262204v2.32","doi-asserted-by":"publisher","DOI":"10.1007\/s00412-007-0097-5"},{"key":"2019071819065895000_262204v2.33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001962"},{"key":"2019071819065895000_262204v2.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.12.009"},{"key":"2019071819065895000_262204v2.35","doi-asserted-by":"crossref","unstructured":"Piskadlo, E. , A. Tavares , and R.A. Oliveira . 2017. Metaphase chromosome structure is dynamically maintained by condensin I-directed DNA (de)catenation. Elife. 6.","DOI":"10.7554\/eLife.26120"},{"key":"2019071819065895000_262204v2.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.08.007"},{"key":"2019071819065895000_262204v2.37","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201607022"},{"key":"2019071819065895000_262204v2.38","doi-asserted-by":"crossref","first-page":"39118","DOI":"10.1038\/srep39118","article-title":"Naa50\/San-dependent N-terminal acetylation of Scc1 is potentially important for sister chromatid cohesion","volume":"6","year":"2016","journal-title":"Sci Rep."},{"key":"2019071819065895000_262204v2.39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.737585"},{"key":"2019071819065895000_262204v2.40","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2019071819065895000_262204v2.41","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cub.2006.11.051","article-title":"Incorporation of Drosophila CID\/CENP-A and CENP-C into Centromeres during Early Embryonic Anaphase","volume":"17","year":"2007","journal-title":"Current biology : CB"},{"key":"2019071819065895000_262204v2.42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.302406"},{"key":"2019071819065895000_262204v2.43","doi-asserted-by":"publisher","DOI":"10.1038\/35019529"},{"key":"2019071819065895000_262204v2.44","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.107.080408"},{"key":"2019071819065895000_262204v2.45","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.cels.2017.05.003","article-title":"Stochastic Modeling Yields a Mechanistic Framework for Spindle Attachment Error Correction in Budding Yeast Mitosis","volume":"4","year":"2017","journal-title":"Cell Syst."},{"key":"2019071819065895000_262204v2.46","doi-asserted-by":"publisher","DOI":"10.1038\/21831"},{"key":"2019071819065895000_262204v2.47","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00130-6"},{"key":"2019071819065895000_262204v2.48","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/j.cub.2003.11.018","article-title":"Two putative acetyltransferases, san and deco, are required for establishing sister chromatid cohesion in Drosophila","volume":"13","year":"2003","journal-title":"Current biology : CB"},{"key":"2019071819065895000_262204v2.49","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.cub.2005.03.019","article-title":"Efficient chromosome capture requires a bias in the \u2018search-and-capture\u2019 process during mitotic-spindle assembly","volume":"15","year":"2005","journal-title":"Current biology : CB"},{"key":"2019071819065895000_262204v2.50","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1242\/dev.129.10.2411","article-title":"Repression of Teashirt marks the initiation of wing development","volume":"129","year":"2002","journal-title":"Development"},{"key":"2019071819065895000_262204v2.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2013.05.005"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/262204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T21:54:26Z","timestamp":1768427666000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/262204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,8]]},"references-count":51,"URL":"https:\/\/doi.org\/10.1101\/262204","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.cub.2018.06.062","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2018,2,8]]},"subtype":"preprint"}}