# Initiation of DNA Replication at Cell Origins in Yeast

> **NIH NIH R01** · COLD SPRING HARBOR LABORATORY · 2022 · $751,488

## Abstract

The goal of this research is to determine the mechanism and regulation of the initiation of DNA
replication in eukaryotic cells. It is clear that for maintenance of the integrity of the genome from
one cell generation to the next, DNA and its associated chromatin structures must be duplicated
in a highly controlled and accurate manner. Interruption of these controls may promote genome
instability and lead to neoplastic transformation in somatic cells or result in mutations in the germ
line that can cause many different disorders. Moreover, the DNA replication proteins represent
tangible targets for therapeutic intervention and diagnosis of proliferation of cancer cells and other
proliferative disorders. The initiator protein (ORC) cooperates with a series of DNA replication
proteins, including Cdc6, Cdt1 and the MCM2-7 hexamer to establish at origins of DNA replication
a pre-Replicative Complex (pre-RC) that facilitates later initiation of DNA synthesis at each origin.
Recent progress has determined the mechanism of assembly of the pre-RC and the structure
of its components. The proposed research in this application will investigate, using proteins from
multiple yeast species and human cells, how origins of DNA replication are specified in these
diverse genomes. One of them, the yeast S. cerevisiae has DNA sequence specific origins but
the others do not; therefore we propose to determine how these other eukaryotes specify and
control DNA replication origins.

## Key facts

- **NIH application ID:** 10521809
- **Project number:** 2R01GM045436-29A1
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** BRUCE W. STILLMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $751,488
- **Award type:** 2
- **Project period:** 1991-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10521809

## Citation

> US National Institutes of Health, RePORTER application 10521809, Initiation of DNA Replication at Cell Origins in Yeast (2R01GM045436-29A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10521809. Licensed CC0.

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