# Deciphering real-time dynamics of the human genome organization in response to DNA damage and gene expression

> **NIH NIH R00** · OHIO STATE UNIVERSITY · 2020 · $249,000

## Abstract

PROJECT SUMMARY
The human genome is highly organized and regulated to express cell-type and tissue-specific genes. During
interphase, chromosomes occupy distinct regions in the nucleus, known as chromosome territories, a concept
proposed as early as 1885 and demonstrated in 1982. Technological developments over the last two decades
have allowed changes in the three-dimensional architecture of the genome to be examined and modeled. But
understanding the mechanisms that localize or mobilize chromosomal loci in the nucleus will require high-
resolution studies in real time. The recent development of CRISPRainbow allows the simultaneous labeling,
visualization, and real-time tracking of up to seven specific genomic loci at high resolution in live human cells.
Preliminary studies show that loci on homologous and non-homologous chromosomes move with different
speeds, directions, and confinement. CRISPRainbow allows quantitative categorization of the movements of
various loci, detects accelerated movements at DNA double-strand breaks, and change in a chromosome's
overall organization. The goal of this proposal is to answer the following questions. What is spatial range of
genomic loci movements? Is the dimension of the dynamic spatial range chromosome-specific and/or
dependent of its intranuclear localization? How does long-range chromatin territory relocation take place
following DNA double-strand breaks? What is the interplay of transcription and the chromatin remodelers on
genomic loci movements and entire chromatin organization changes? During the K99 phase, CRISPR-based
single-molecule real-time microscopy will be used to quantitatively image and characterize genomic loci
movements and to test the hypothesis that genomic loci movements depend on chromosome identity or on
nuclear location. Chromatin territory relocation will also be tracked during DNA damage repair in single cells.
During the R00 phase, chromosome conformation capture experiments will be used to molecularly
characterize changes in chromosomal interactions upon DNA damage and molecular, cellular, and genetic
experiments will be used to investigate chromatin dynamics in response to transcription activation/silencing,
nucleosome disassembly, and the tumor suppressor p53. This proposal is highly interdisciplinary, will shed the
light on human genome organization and stability, and will lead to powerful quantitative real-time methodology
to investigate mechanisms of chromosome translocation in cancer cells. This study draws on expertise from
mentors who are leaders in the field of single-molecule real-time microscopy, nuclear biology, and
genome/nuclear architecture and who will help prepare Dr. Tu for a transition to a career as an independent
investigator.

## Key facts

- **NIH application ID:** 9889153
- **Project number:** 5R00GM126810-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Li-Chun Tu
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889153

## Citation

> US National Institutes of Health, RePORTER application 9889153, Deciphering real-time dynamics of the human genome organization in response to DNA damage and gene expression (5R00GM126810-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9889153. Licensed CC0.

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