# Centromere identity, strength, and regulation

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2020 · $563,113

## Abstract

Project Summary/Abstract
Defects in the equal partitioning of chromosomes at cell division causes aneuploidy, a genetic catastrophe that
results in spontaneous abortion or birth defects if it arises in the gametes and that is a major contributor to
gene dosage imbalances in almost all human cancers. The centromere is the locus on each chromosome that
directs accurate chromosome segregation at cell division in healthy cells, but a paradox exists in the field
because the DNA sequences typically found at the loci are neither necessary nor sufficient for centromere
function. As our major area of contribution to science, thus far, we have made major headway during the past
decade in elucidating the molecular basis for centromere identity, the epigenetic pathway that propagates
centromeric chromatin in perpetuity, the relationship between epigenetic and genetic information in driving
centromere evolution in eukaryotes, and key steps in the quality control pathway that ensures proper
chromosome segregation at cell division. In the next five years, we are poised to make quantum leaps in our
molecular understanding of centromeres in three areas. The first area is with a new type of human artificial
chromosome (HAC) that we have recently developed. We will gain new insight regarding the relationship
between DNA sequence and centromere formation and expand the utility of HACs in experimental and applied
settings. The second area is with mouse models and biochemical reconstitution to expand our understanding
of the balance of epigenetics and genetics at the centromere. We will build on our success with gaining the first
molecular evidence in mammals of an evolutionary process known as “centromere drive” to now define the
relationship of this process to the expansion of centromeric satellite DNA sequences. In addition, we will
investigate the role of the centromere repeats typically found at human centromeres on the physical properties
of centromeric chromatin using purified components. The third area is with a combination of biophysical, cell
biological, and epigenomic approaches to extend our understanding of centromere regulation at mitosis. We
will focus on the chromatin at the “inner centromere” (i.e. between the pair of sister centromeres on a mitotic
chromosome) that plays a key role in the quality control step known as mitotic error correction. Altogether, our
progress in these three areas will constitute a major advance in our understanding of the molecular
mechanisms underlying the specification and regulation of centromeres.

## Key facts

- **NIH application ID:** 9896871
- **Project number:** 5R35GM130302-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ben E. Black
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $563,113
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896871

## Citation

> US National Institutes of Health, RePORTER application 9896871, Centromere identity, strength, and regulation (5R35GM130302-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9896871. Licensed CC0.

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