# Biophysics of Nuclear Formation and Micronucleation

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2021 · $70,458

## Abstract

Project Summary/Abstract
The cell nucleus of higher eukaryotic cells undergoes a dynamic process of disassembly and reassembly
during the open mitosis. Failing to reform a single nucleus encasing the entire set of chromosomes often
results in small extranuclear bodies, referred to as micronuclei. Micronuclei are prone to irreversible rupture
and catastrophic DNA damages, which has been largely implicated in cancer. Recent works have suggested
that barrier-to-autointegration factor (BAF/BANF1) crosslinks DNA to a single mass, thereby guiding nuclear
membranes to bridge across chromosomes. However, further investigation is necessary to understand detailed
biophysical mechanism of action by which BAF mediates nuclear membranes. Previous studies and
preliminary data led to the hypothesis of this study that BAF may form fiber-like structures, beyond simple
dimers, that connect and congress distant chromosomes. The goal of the proposed study is to investigate this
possibility and its implications in nuclear envelope formation. To this end, the first aim is to develop a
biophysical assay using Xenopus egg extract and micro-patterned DNA to scrutinize the bridging of nuclear
envelope across gaps between chromosomes, and quantitatively dissect the role of BAF complex during this
process. In the next aim, 3D dynamics of the fiber-like structures of BAF during nuclear formation will be
analyzed in living cells, using lattice light-sheet microscopy and molecular perturbation techniques. Finally,
DNA binding and polymerization dynamics of BAF revealed in the extract system and living cells will be
reconstituted in a simplest system of purified components to further investigate the biophysical basis.
Consequently, the proposed study will offer the mechanistic insight into nuclear formation and micronucleation
and establish the foundation for mathematical modeling of these processes. Furthermore, the results have the
potential to expand our understanding of cancer micronuclei, thereby aiding in the development of novel
cancer therapy and diagnostics. Conducting the proposed study, the applicant aims to deepen his expertise in
quantitative biology and microscopy, while at the same time, expanding the breadth of his skills and intellectual
horizon to reconstituted cell-free systems and translational research. This project will benefit from the highly
interdisciplinary research environment of the Systems Biology department at Harvard Medical School along
with the sponsor’s strong support.

## Key facts

- **NIH application ID:** 10220079
- **Project number:** 5F32GM131585-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Tae Yeon Yoo
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,458
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220079

## Citation

> US National Institutes of Health, RePORTER application 10220079, Biophysics of Nuclear Formation and Micronucleation (5F32GM131585-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10220079. Licensed CC0.

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