# How bacterial SMC complexes organize chromosomes

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $329,365

## Abstract

Project Summary
The organization and segregation of replicated chromosomes are fundamental to living systems. Structural
maintenance of chromosomes (SMC) complexes play central roles in these processes in all domains of life.
These ring-shaped ATPases share common structures and inter-subunit contacts, consistent with a common
mechanism of action. Over the last five years, studies in Bacillus subtilis and eukaryotes have provided
compelling in vivo and in vitro evidence that SMC complexes utilize ATP hydrolysis to extrude DNA loops. In the
case of B. subtilis, SMC condensin complexes are loaded at centromeric parS sites near the replication origin,
then translocate down the left and right chromosome arms, tethering them together. In this way, condensins
generate a single chromosome loop centered on the origin that draws sister chromosomes in on themselves and
away from each other. This elegantly simple loop-extrusion model provides a unifying mechanism to explain how
eukaryotic SMC cohesin complexes form topologically associating domains (TADs) in interphase, how eukaryotic
SMC condensin complexes compact DNA into rod-shaped sister chromatids, and how bacterial SMC condensins
resolve newly replicated origins. However, this model raises an important question: how do SMC complexes
extrude DNA loops when the chromosome is coated by numerous proteins and acted upon by replication and
transcription machineries? And how are the topologically loaded complexes released from the chromosome?
The goal of this proposed research is to understand the mechanism of condensin action in the context of cellular
activities, taking advantage of the many molecular and cytological tools we have developed. First, we will
determine how condensins act when they encounter the replisome or other condensin molecules. Second, we
will characterize how condensins are released from the chromosome when they reach the terminus region.
Finally, we will explore condensin’s role in the organization and dynamics of a multipartite bacterial genome that
contains both a circular and a linear chromosome. Taken together, the proposed work has the potential to provide
the general principles of chromosome folding and compaction in all organisms.

## Key facts

- **NIH application ID:** 10841027
- **Project number:** 5R01GM141242-04
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Xindan Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $329,365
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841027

## Citation

> US National Institutes of Health, RePORTER application 10841027, How bacterial SMC complexes organize chromosomes (5R01GM141242-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10841027. Licensed CC0.

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