# Regulation of Chromosome Segregation

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $352,000

## Abstract

Project Summary/Abstract
Accurate cell division is critical for the proliferation and development of organisms. The precise partitioning of
duplicated chromosomes to daughter cells is an essential event in the cell cycle. Defects in chromosome
segregation lead to aneuploidy, the state where entire chromosomes are gained or loss. Aneuploidy is a the
most common chromosomal abnormality in cancer cells and has been postulated to be a major factor in the
evolution of cancer. It is also the leading cause of spontaneous miscarriages and hereditary birth defects in
humans. The proposed work will lead to an understanding of the mechanisms that ensure accurate
chromosome segregation and thus maintain genomic stability and prevent human disease. Chromosome
segregation requires forces generated by spindle microtubules that are translated into chromosome movement
through interactions with kinetochores, the highly conserved structures that assemble onto centromeric
chromatin. Accurate segregation requires kinetochores to maintain load-bearing attachments to the ends of
microtubules that are continually growing and shrinking. Kinetochores must also biorient and attach to
microtubules from opposite poles. When there is a defect in biorientation, error correction systems destabilize
improper attachments. In the next funding period, this proposal will use in vitro assays to address a number of
outstanding questions about kinetochore assembly and function. 1) How is kinetochore assembly regulated? 2)
How do outer kinetochore proteins contribute to force-dependent kinetochore-microtubule attachments? 3)
How is the Aurora B error correction pathway regulated by tension? The proposal will use budding yeast for
these studies because they are amenable to biochemical, genetic and cytological studies, and the yeast
kinetochore is the best characterized to date. Taken together, these studies of kinetochores in budding yeast
will lead toward an understanding of the fundamental mechanisms of segregation in all eukaryotes.

## Key facts

- **NIH application ID:** 9993537
- **Project number:** 5R01GM064386-19
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Susan Biggins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,000
- **Award type:** 5
- **Project period:** 2002-02-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993537

## Citation

> US National Institutes of Health, RePORTER application 9993537, Regulation of Chromosome Segregation (5R01GM064386-19). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/9993537. Licensed CC0.

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