# Chromosome Dynamics in Bacillus Subtills

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2021 · $372,900

## Abstract

Compaction and resolution of replicated chromosomes into morphologically and spatially distinct sister
chromatids is essential for faithful DNA segregation in all organisms, but the molecular mechanisms that
underlie these processes are poorly understood. In bacteria, chromosome segregation is largely driven by
DNA compaction, which is thought to occur by the orderly folding of chromosomes along adjacent DNA
segments drawing replicated sisters in on themselves and away from each other. In virtually all organisms,
Structural Maintenance of Chromosomes (SMC) condensin complexes play a central role in this process but
how these ring-shaped ATPase function has remained unclear.
In Bacillus subtilis, condensin rings are topologically loaded onto the chromosome adjacent to the origin of
replication by the partitioning protein ParB bound to centromeric parS sites. Using chromosome conformation
capture (Hi-C) and ChIP-seq, we discovered that these complexes then travel down the left and right
chromosome arms all the way to the terminus while tethering the two arms together. Our findings support a
generalizable model in which SMC complexes act along adjacent DNA segments by processively enlarging
DNA loops. In this model, these ring-shaped complexes encircle the DNA flanking their loading site, tethering
the duplexes together. As these tethers move away from their loading sites they generate loops. Loop-
formation ensures that these complexes act along adjacent DNA segments and therefore resolve rather than
tangle sister chromosomes. In B. subtilis, processive loop enlargement centered on origin-proximal parS sites
draws sister origins in on themselves and away from each other. De novo loop formation along chromosome
arms in eukaryotes can also explain how condensin complexes compact and resolve sister chromatids during
mitosis and provides a mechanism for the formation of transcriptionally insulated domains (also called
topologically associated domains or TADs) by SMC cohesin complexes during interphase. Our studies on the
B. subtilis SMC complex highlights the importance of using simple model systems to study conserved cell
biological processes. The experiments described in this proposal build on our recent discoveries and
preliminary findings to define how these broadly conserved complexes generate DNA loops; how these ring-
shaped tethers are removed when they reach the replication terminus; and the role of condensin in
remodeling the bacterial chromosome during the replication-segregation cycle.

## Key facts

- **NIH application ID:** 10153802
- **Project number:** 5R01GM086466-12
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** DAVID Z RUDNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $372,900
- **Award type:** 5
- **Project period:** 2009-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153802

## Citation

> US National Institutes of Health, RePORTER application 10153802, Chromosome Dynamics in Bacillus Subtills (5R01GM086466-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10153802. Licensed CC0.

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