# Mechanisms to move and steer chromosomes

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $323,000

## Abstract

Project Summary/Abstract
We will elucidate the mechanisms that power the movements of chromosomes on the mitotic spindle and the
mechanisms that control the direction of these movements. Fungi use the ring shaped Dam1 complex, which
works with multiple “arm-like” Ndc80 complexes to move chromosomes. This ring can be pushed poleward by
a “power stroke” generated when depolymerizing microtubules curve at the plus end to power the movement of
chromosomes. However, it is unclear how most eukaryotes, including humans, power chromosome movement
since they lack the Dam1 ring complex. We visualized purified human Ndc80 and Ska complexes on
microtubules by EM tomography to elucidate the structure of the human kinetochore-microtubule attachment.
These new structures orient Ska on microtubules and also suggest Ndc80 complexes oligomerize on
microtubules to form a structure we have named the “sliding foot”. This new structure suggests testable
mechanisms for how metazoans kinetochores are pushed by the curvature of a depolymerizing microtubule
like yeast. We have developed two in vivo assays that allow us to measure the formation of the sliding feet
and to measure the chromosome movements that require Ska. In addition, we will employ single molecule
assays to measure the requirement of the sliding foot to generate force in vitro. Using these new assays, we
will identify the mechanism that powers the movements of human chromosomes on the mitotic spindle.
Surprisingly, on most chromosomes only one of the two sister kinetochores has sliding feet. This is exciting
because chromosome movements require one sister to actively engage depolymerizing ~20 microtubules to
pull chromosomes, while its sister must passively attach to growing microtubules. We will identify the
regulatory pathways that generate the asymmetry of sliding foot formation on the two sister kinetochores. We
hypothesize that these pathways not only regulate sliding foot formation but can also ensure that one sister
has depolymerizing microtubules while the microtubules bound to its sister kinetochore are polymerizing. We
will build on these findings to identify the mechanisms that direct chromosome movements either towards or
away from poles on the mitotic spindle.
It is important to understand these basic mechanisms that lie at the center of the chromatid segregation to
determine how cancer cells lower the fidelity of mitosis to generate genomic instability and to increase the
efficacy of anti-tubulin chemotherapeutics.

## Key facts

- **NIH application ID:** 10214634
- **Project number:** 5R01GM124042-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** P. TODD STUKENBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214634

## Citation

> US National Institutes of Health, RePORTER application 10214634, Mechanisms to move and steer chromosomes (5R01GM124042-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214634. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*