# Binding, Sliding and Function of Cohesin on Sister Chromatids

> **NIH NIH R01** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2021 · $387,319

## Abstract

PI: Gartenberg, Marc R.
PROJECT SUMMARY
Cohesin organizes eukaryotic genomes into structures that segregate faithfully between dividing cells. The
complex keeps newly replicated sister chromatids together and folds individual chromatids into compact
chromosomal structures. Cohesin accomplishes these tasks by holding distant DNA sites in close proximity.
Defects in cohesin or cohesin regulators have been linked to cancer and are the cause of developmental
diseases known collectively as cohesinopathies. Thus, understanding how cohesin functions will reveal much
about chromosome structure as it relates to human health.
Cohesin complexes bind numerous chromosomal sites by encircling the DNA of each site in a topological
embrace. Many cohesin binding sites lie in and around genes. When the genes are expressed, cohesin must
move out of the way of advancing RNA polymerases. How this occurs is not clear. The central goal of this
proposal is to understand how cohesin moves on chromosomal arms to adopt positions that achieve structural
roles yet permit proper gene expression.
The Gartenberg lab recently showed that cohesin translocates on DNA by sliding, and that the complex
remains cohesive while in motion. Using yeast as a model system, this proposal aims to determine how the
dynamic distribution of cohesin on chromosomal DNA is determined by binding, sliding and function of the
complex. Aim 1 uses novel, molecular biology assays to define the dimensions of the DNA channel through
cohesin, as well as determine whether the complex embraces one or two chromatids within the same channel.
The experiments will determine how the dimensions of the complex limit which obstacles the complex can slide
past. Aim 2 uses molecular biology assays to determine how transcription and other ATP-dependent
processes regulate cohesin movement, and define the biological consequences when movement is blocked.
The experiments will determine the molecular basis and physiological benefit of cohesin accumulating at
specific cohesin enrichment sites. Aim 3 uses genome-scale strategies to distinguish between chromosomal
sites where cohesin holds sister chromatids together and where it does not. The experiments will yield the first
comprehensive maps of cohesin based on the functionality of the complex.

## Key facts

- **NIH application ID:** 10107672
- **Project number:** 5R01GM051402-23
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** Marc R. Gartenberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $387,319
- **Award type:** 5
- **Project period:** 1994-09-12 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107672

## Citation

> US National Institutes of Health, RePORTER application 10107672, Binding, Sliding and Function of Cohesin on Sister Chromatids (5R01GM051402-23). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10107672. Licensed CC0.

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