PT - JOURNAL ARTICLE AU - Cai Tong Ng AU - Li Deng AU - Chen Chen AU - Hong Hwa Lim AU - Jian Shi AU - Uttam Surana AU - Lu Gan TI - A multi-scale model of the yeast chromosome-segregation system AID - 10.1101/299487 DP - 2018 Jan 01 TA - bioRxiv PG - 299487 4099 - http://biorxiv.org/content/early/2018/04/11/299487.short 4100 - http://biorxiv.org/content/early/2018/04/11/299487.full AB - In dividing cells, depolymerizing spindle microtubules move chromosomes by pulling at their kinetochores. While kinetochore subcomplexes have been studied extensively in vitro, little is known about their in vivo structure and interactions with microtubules or their response to spindle damage. Here we combine electron cryotomography of serial cryosections with genetic and pharmacological perturbation to study the yeast chromosome-segregation machinery at molecular resolution in vivo. Each kinetochore microtubule has one (rarely, two) Dam1C/DASH outer-kinetochore assemblies.Dam1C/DASH only contacts the flat surface of the microtubule and does so with its flexible “bridges”. In metaphase, 40% of the Dam1C/DASH assemblies are complete rings; the rest are partial rings. Ring completeness and binding position along the microtubule are sensitive to kinetochore attachment and tension, respectively. Our study supports a model in which each kinetochore must undergo cycles of conformational change to couple microtubule depolymerization to chromosome movement.AbbreviationsMTmicrotubulekMTkinetochore microtubulecryo-ETelectron cryotomography / cryo-electron tomography