# The role of Orc6 in DNA replication and cytokinesis

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $70,000

## Abstract

Abstract.
 The Origin Recognition Complex (ORC), heteromeric six-subunit protein
complex, is essential for DNA replication. ORC's functions also extend beyond DNA
replication. We found that the smallest of ORC subunit, Orc6 protein, is important for
DNA binding and replication and has a structural homology with transcription factor
TFIIB suggesting that it may target the formation of pre-replicative complex to the
origins of DNA replication. Furthermore, we identified conserved motif within the C-
terminus of Orc6 which is responsible for its interaction with the core ORC complex.
Mutations in this motif affect the integrity of six-subunit ORC contributing to the
pathogenesis of Meier-Gorlin syndrome (MGS) in humans. Orc6 also has a function in
cytokinesis. It binds directly to septin complex via its Pnut subunit, stimulates the
intrinsic GTPase activity of the Drosophila septin complex and greatly facilitates septin
filament formation. The overall goal of our proposal is to characterize the mechanism
of Orc6 functions in DNA replication and cytokinesis using Drosophila as a model
system. Our experiments are designed to answer important questions about the
structure of Orc6, its functions in replication and its role in septin polymerization.
Drosophila model systems will be used to analyze the effects of naturally occurring
and structure-guided targeted mutations of human Orc6 in diverse protein functions.
Because ORC is conserved in evolution, what we learn about its functions in
Drosophila will be valuable to our understanding of ORC's functions in other
eukaryotes. A better understanding of how ORC functions in Drosophila will provide
insights into ORC's behavior in mammals and provide clues as to how its
misregulation leads to cancer.

## Key facts

- **NIH application ID:** 10131388
- **Project number:** 3R01GM121449-04S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** IGOR N CHESNOKOV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,000
- **Award type:** 3
- **Project period:** 2017-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131388

## Citation

> US National Institutes of Health, RePORTER application 10131388, The role of Orc6 in DNA replication and cytokinesis (3R01GM121449-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10131388. Licensed CC0.

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