A stochastic model for error correction of kinetochore-microtubule attachments in budding yeast

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dc.contributor.authorBanerjee, Ananden
dc.contributor.authorAdames, Neil R.en
dc.contributor.authorPeccoud, Jeanen
dc.contributor.authorTyson, John J.en
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2020-10-07T17:45:18Zen
dc.date.available2020-10-07T17:45:18Zen
dc.date.issued2020-08-06en
dc.description.abstractTo divide replicated chromosomes equally between daughter cells, kinetochores must attach to microtubules emanating from opposite poles of the mitotic spindle (biorientation). An error correction mechanism facilitates this process by destabilizing erroneous kinetochore-microtubule attachments. Here we present a stochastic model of kinetochore-microtubule attachments, via an essential protein Ndc80 in budding yeast,Saccharomyces cerevisiae. Using the model, we calculate the stochastic dynamics of a pair of sister kinetochores as they transition among different attachment states. First of all, we determine the kinase-to-phosphatase balance point that maximizes the probability of biorientation, while starting from an erroneous attachment state. We find that the balance point is sensitive to the rates of microtubule-Ndc80 dissociation and derive an approximate analytical formula that defines the balance point. Secondly, we determine the probability of transition from low-tension amphitelic to monotelic attachment and find that, despite this probability being approximately 33%, biorientation can be achieved with high probability. Thirdly, we calculate the contribution of the geometrical orientation of sister kinetochores to the probability of biorientation and show that, in the absence of geometrical orientation, the biorientation error rate is much larger than that observed in experiments. Finally, we study the coupling of the error correction mechanism to the spindle assembly checkpoint by calculating the average binding of checkpoint-related proteins to the kinetochore during the error correction process.en
dc.description.notesResearch reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM078989, to JP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.description.sponsorshipNational Institute of General Medical Sciences of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM078989]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0236293en
dc.identifier.issn1932-6203en
dc.identifier.issue8en
dc.identifier.othere0236293en
dc.identifier.pmid32760074en
dc.identifier.urihttp://hdl.handle.net/10919/100303en
dc.identifier.volume15en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleA stochastic model for error correction of kinetochore-microtubule attachments in budding yeasten
dc.title.serialPlos Oneen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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