# Organization of the Mammalian Mitotic Spindle

> **NIH NIH R37** · DARTMOUTH COLLEGE · 2021 · $676,254

## Abstract

Accurate chromosome segregation is essential for the propagation of species and the viability of cells, and is
driven by a complex microtubule-based structure called the spindle. Intensive biochemical, genetic, and
proteomic efforts provide an extensive catalogue of proteins that participate in spindle organization and
spindle-dependent chromosome movement. However, these efforts don't reveal the molecular mechanisms
that ensure faithful chromosome segregation in mammalian cells. Recently, we showed that the most
common cause of chromosome mis-segregation in human tumor cells is the persistence of kinetochore-
microtubule (k-MT) attachment errors. This indicates that the most important mechanism ensuring faithful
chromosome segregation is the fine-tuning of k-MT attachment stability, yet our understanding for how k-MT
attachment stability is regulated during mitosis is starkly incomplete. We don't understand how the
stabilizing and destabilizing components work in concert to generate a coherent k-MT attachment stability at
different phases of mitosis. We also don't understand how aneuploidy influences genome stability and cell
survival. Based on models generated during the current funding period, it is our goal in the forthcoming
funding period to combine biochemical methods and live cell imaging to test models and determine the
mechanisms of the regulation of K-MT attachments in mitosis. Understanding these mechanisms could lead
to new therapeutic approaches for cancer treatment.
RELEVANCE (See instructions):
Errors in chromosome segregation cause aneuploidy that causes birth defects and is commonly associated
with advanced stage cancer. The goal of the experiments proposed here is to identify the proteins and
determine the mechanisms responsible for high fidelity chromosome segregation in human cells. Data
generated from this work will provide insight into mechanisms of aneuploidy in tumor cells and may reveal
strategies for therapy of chromosomally unstable aneuploid tumors.

## Key facts

- **NIH application ID:** 10107830
- **Project number:** 5R37GM051542-25
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Duane A. Compton
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $676,254
- **Award type:** 5
- **Project period:** 1996-08-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107830

## Citation

> US National Institutes of Health, RePORTER application 10107830, Organization of the Mammalian Mitotic Spindle (5R37GM051542-25). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10107830. Licensed CC0.

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