# Activities of nucleoprotein complexes visualized in single-molecule experiments

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $363,502

## Abstract

Project Summary
Mechanistic understanding of living things requires our understanding of how proteins and DNA interact
together to generate functional chromosomes. This understanding is central to preserving human health,
dealing with genetic disorders, and fighting pathogenic organisms. The proposed projects are focused on
single-molecule analyses which permit direct visualization of biomolecule interactions, and can be used to
analyze protein-DNA interactions in detail. The aims of the proposal include careful study of a facilitated
dissociation "exchange" mechanism for removal of proteins from DNA that suggests a major revision of
conventional descriptions of protein turnover on DNA, and which will affect a wide range of studies of gene
regulatory and chromosome structural proteins. The second and third aims are focused on study of
mechanisms of large "Structural Maintenance of Chromosomes" (SMC) protein complexes which mediate the
folding of chromosomes in eukaryote cells. The second aim concerns understanding the mechanics of
compaction and DNA substrate selection by the Smc5/6 complex, which plays a key role in separating
replicated chromosomes from one another during cell division, while the third aim concerns direct microscopy
observation of the mechanism by which Smc5/6 compacts DNA. The second and third aim will also include
side-by-side comparisons of Smc5/6 and the more well-understood condensin complex. The highly
mechanistic analyses of DNA processing machinery that are proposed will give us a stronger understanding of
how cells interpret, fold and change their genomes, leading to a better understanding of pathologies where
those functions are impaired, and better understanding of how to target those functions in pathogenic
organisms.

## Key facts

- **NIH application ID:** 10732763
- **Project number:** 5R01GM105847-07
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JOHN F MARKO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $363,502
- **Award type:** 5
- **Project period:** 2013-09-30 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10732763

## Citation

> US National Institutes of Health, RePORTER application 10732763, Activities of nucleoprotein complexes visualized in single-molecule experiments (5R01GM105847-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10732763. Licensed CC0.

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