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A multi-scale model of the yeast chromosome-segregation system

Ng, Cai Tong and Deng, Li and Chen, Chen and Lim, Hong Hwa and Shi, Jian and Surana, Uttam and Gan, Lu (2018) A multi-scale model of the yeast chromosome-segregation system. . (Unpublished) http://resolver.caltech.edu/CaltechAUTHORS:20181030-155636439

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Abstract

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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/299487DOIDiscussion Paper
ORCID:
AuthorORCID
Ng, Cai Tong0000-0002-1082-8667
Lim, Hong Hwa0000-0002-0951-7220
Shi, Jian0000-0003-3810-5302
Surana, Uttam0000-0002-4785-6514
Gan, Lu0000-0002-8685-4896
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. bioRxiv preprint first posted online Apr. 11, 2018. We thank the CBIS microscopy staff for support and training, Gemma An for suggesting the use of parallel-bar grids, Shujun Cai for helping with cryo-EM, Simon Jenni and Steve Harrison for Dam1C/DASH plasmids and sharing results prior to publication, Jeff Yong for advice on chromatography, the Jensen lab for computer access, and members of the Gan group, Jack Johnson, Steve Harrison and Paul Matsudaira for feedback. CTN, CC, LD, and LG were funded by NUS startups R-154-000-515-133, R-154-000-524-651, and D-E12-303-154-217, an MOE T2 R-154-000-624-112, with equipment support from NUS YIA R-154-000-558-133. HHL and US were funded by the Biomedical Research Council of A*STAR (Agency of Science Technology and Research), Singapore. Author Contributions: CTN - experiments, project design, writing, LD - experiments, CC - project design, experiments, HHL - experiments, JS - training, US - project design, writing, LG - experiments, project design, writing.
Funders:
Funding AgencyGrant Number
National University of SingaporeR-154-000-515-133
National University of SingaporeR-154-000-524-651
National University of SingaporeD-E12-303-154-217
Ministry of Education (Singapore)T2 R-154-000-624-112
National University of SingaporeYIA R-154-000-558-133
Agency for Science, Technology and Research (A*STAR)UNSPECIFIED
Record Number:CaltechAUTHORS:20181030-155636439
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20181030-155636439
Official Citation:A multi-scale model of the yeast chromosome-segregation system. Cai Tong Ng, Li Deng, Chen Chen, Hong Hwa Lim, Jian Shi, Uttam Surana, Lu Gan. bioRxiv 299487; doi: https://doi.org/10.1101/299487
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90529
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:30 Oct 2018 23:12
Last Modified:23 Apr 2019 21:15

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