# Origin Recognition Complex and Transcriptional Silencers

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $374,850

## Abstract

ABSTRACT
 The accurate and efficient duplication of the eukaryotic genome requires the activation of multiple DNA
replication origins distributed over the length of each chromosome. While each origin has the same basic
purpose—to direct unwinding of the chromosomal DNA for the initiation of DNA synthesis—each must function
within a distinct chromatin context. Despite the well known heterogeneity of chromatin, the field has little
understanding of how the core origin binding proteins function within different chromatin contexts or whether
origin DNA sequence requirements are influenced by chromatin. The work in the lab of Catherine Fox indicates
that these issues are important for explaining why individual origins exhibit differences in how often (origin
efficiency) and when (origin activation time) they function during S-phase. This origin functional diversity
establishes a temporal pattern to chromosomal replication that is crucial to both cell differentiation and genome
stability.
 The proposed research will define mechanisms that underlie origin functional diversity in the model
organism Saccharomyces cerevisiae because the origin-binding proteins and many aspects of chromatin are
conserved. In contrast to early models for how origin-specific functional differences in yeast are achieved, the
Fox lab proposes that chromatin-mediated regulation of ORC-DNA interactions help establish origin functional
diversity. The lab's research provides evidence that ORC-DNA binding in vivo is a target of both positive and
negative regulation by chromatin, depending on context; the proposed research will examine the molecular
mechanism of two evolutionarily conserved positive regulators. The experiments in this proposal will address a
fundamental hypothesis that functionally relevant ORC-origin binding results from a combination of ORC-DNA
and ORC-chromatin interactions that result in origin-specific ORC-DNA dynamics that contribute to the
regulation of origin function in S-phase.

## Key facts

- **NIH application ID:** 9922294
- **Project number:** 5R01GM056890-21
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Catherine A Fox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $374,850
- **Award type:** 5
- **Project period:** 1998-01-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922294

## Citation

> US National Institutes of Health, RePORTER application 9922294, Origin Recognition Complex and Transcriptional Silencers (5R01GM056890-21). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9922294. Licensed CC0.

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