# Genetic and Epigenetic Determinants of Centromere Identity

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $402,500

## Abstract

Project Summary
Centromeres are essential chromosomal elements that mediate kinetochore assembly and accurate
chromosome segregation. Centromere defects lead to chromosome missegregation, with detrimental effects
on cell and organism health and fertility. In most multicellular species, centromeres are composed of large
regions of highly repetitive DNA marked by chromatin containing the centromere-specific histone variant
CENP-A. Previous work demonstrated that both centromeric DNA and CENP-A chromatin have the potential to
initiate centromere activity de novo; however, their respective contributions to centromere specification in
mitosis and meiosis have remained elusive. The overall goal of this proposal is to determine how centromeric
DNA and chromatin contribute to centromere identity. The centromeres of metazoans have been refractory to
full sequencing and assembly due their large size and highly repetitive nature, hampering our ability to
systematically interrogate the role of centromeric DNA elements. Additionally, there are currently no systems in
which to test if de novo centromeres, which are devoid of centromeric DNA, and can sustain centromere
function and specification through mitotic and meiotic divisions. Using our unique advancements in Drosophila,
which include the identification and assembly of its centromeric sequences and the establishment of an
inducible de novo centromere system, this proposal will: 1) test if chromatin-mediated centromeres can sustain
chromosome segregation through development and meiosis, effectively replacing endogenous centromeres; 2)
test specific hypothesis on how centromeric DNA elements may contribute to CENP-A chromatin establishment
or maintenance. Collectively, this work will shed light into centromere specification mechanisms in Drosophila,
an exceptional model system that allows centromere studies in the context of animal development and fertility-
with broad relevance to other species, including humans.

## Key facts

- **NIH application ID:** 9983084
- **Project number:** 5R35GM131868-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** BARBARA MELLONE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983084

## Citation

> US National Institutes of Health, RePORTER application 9983084, Genetic and Epigenetic Determinants of Centromere Identity (5R35GM131868-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983084. Licensed CC0.

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