# Mechanisms Regulating DNA Replication in the Developing Vertebrate Embryo

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2021 · $9,288

## Abstract

Abstract
Great strides are continually made in showing how the initiation of individual replication forks is
regulated, and the next frontier is to understand how DNA replication is coordinated with transcription
and chromatin structure. In particular, little is known about the mechanisms and function of DNA
replication control during vertebrate development, when transcription and chromatin structure are
highly dynamic. This gap in knowledge is an important problem because, until it is filled, the roles for
DNA replication in developmental disorders and cancers associated with epigenetic or DNA
replication deregulation will be largely incomprehensible. With the unique capability of using both
traditional cell culture as well as zebrafish embryos as model systems, we are uniquely poised to
define the key factors in the regulation of replication fork initiation. In this application, we are
requesting funds through an equipment supplement to purchase a replacement biosafety cabinet that
can be used with the Aims of NIH GM121703. The existing biosafety cabinet is over 35 years old and
has become obsolete. All experiments in Aim 3 require the use of a BSL2 biosafety cabinet. This
Aim tests whether early replication of acetylated chromatin depends on the physical interaction of an
essential replication factor, TICRR, and the epigenetic reader protein BRD4. Results from this aim
show that disruption of the TICRR-BRD interaction leads to aberrant timing of replication initiation
during S-phase. To address how specific replication initiation proteins ensure that large genomic
segments are replicated at the correct time, engineered endogenously tagged cell lines of additional
replication factors will be used. Successful achievement of the research in GM121703 is significant
because it seeks to answer fundamental questions about how and why DNA replication initiation
changes throughout development.

## Key facts

- **NIH application ID:** 10387893
- **Project number:** 3R01GM121703-05S1
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** CHRISTOPHER L SANSAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $9,288
- **Award type:** 3
- **Project period:** 2017-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387893

## Citation

> US National Institutes of Health, RePORTER application 10387893, Mechanisms Regulating DNA Replication in the Developing Vertebrate Embryo (3R01GM121703-05S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10387893. Licensed CC0.

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