# Structure and Function of a Eukaryotic Centromere

> **NIH NIH R37** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $497,362

## Abstract

The long term goal of my laboratory is to understand the mechanisms responsible for chromosome
segregation. Accurate chromosome segregation is essential for normal growth and development. Errors in
segregation lead to Down's syndrome, the most frequent inherited birth defect, pregnancy loss, and cancer.
Age-related errors in maintaining the ends of chromosomes (telomeres) have been long recognized as a
cause of replicative senescence. More recently, loss of centromere cohesin and the inability to bind meiotic
chromosomes together has been directly linked to mechanisms responsible for the maternal age affect
wherein the probability of a trisomic pregnancy increases from 2% to 35% by the age of 40.
We have identified a novel structure composed of cohesin, condensin and pericentric DNA that
encompasses the spindle microtubules in metaphase in the model organism, S. cerevisiae. The chromatin
barrel acts as a spring in mitosis that contributes to force balance mechanisms when chromosome
attachment and alignment are monitored by the spindle checkpoint. We have recently discovered a
mechanism in which centromere chromatin loops generate an extensional force sufficient to release
nucleosomes proximal to the spindle axis. The discovery comes from applying thermodynamic principles to
the close packing of radial loops in the centromere. Radial loops are recognized as the structural basis for
the organization of chromosomes in nearly all eukaryotes. The density of loops has biological consequences
that transcend the centromere. Tension forces from closely packed loops impact the affinity of DNA binding
proteins and thus the biochemistry of transcriptional control as well as replication. Our goal is to extend our
understanding of how DNA loops are built, the consequences of close packing, and the implications in
regulating access to the genome. We use the budding yeast with a combination of genetics, quantitative
imaging, in vivo biophysics and computational modeling.
RELEVANCE (See instructions);
The genome of every organism is packaged into chromosomes that must be replicated and segregated
with exquisite fidelity. We have discovered a new structure composed of cohesin and condensin that
surrounds the mitotic spindle. Our work will examine how pericentric chromatin is organized in the spindle
and how it functions in mitosis, a conserved process in all eukaryotes.

## Key facts

- **NIH application ID:** 9983748
- **Project number:** 5R37GM032238-34
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kerry S Bloom
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $497,362
- **Award type:** 5
- **Project period:** 1983-07-01 → 2022-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983748

## Citation

> US National Institutes of Health, RePORTER application 9983748, Structure and Function of a Eukaryotic Centromere (5R37GM032238-34). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983748. Licensed CC0.

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