# Molecular basis of bacterial chromosome segregation and organization

> **NIH NIH R35** · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · 2021 · $363,386

## Abstract

PROJECT SUMMARY/ABSTRACT
A fundamental problem in cell biology is understanding how DNAs are structured by compaction in the densely
packed cellular environment, and accurately passed down to daughter cells. Chromosome-associated proteins
are key factors in dynamically and accurately organizing chromosomes, and directly influence the replication,
transcription, and translation of genetic information. As such, many diseases including various cancers are linked
to malfunctioning of chromosome-associated proteins. In a majority of bacteria, ParABS partitioning system and
structural maintenance of chromosomes (SMC) protein complex are main contributors for chromosome
segregation and organization. The ParABS system is composed of ATPase variant ParA, short palindromic DNA
sequence parS, and parS-binding protein ParB. The parS sites are located in the vicinity of bacterial origin of
replication. A longstanding conundrum in the chromosome biology field is that ParB proteins are not only found
on the parS sites but also associate extensive (10-20 kb) flanking regions – a phenomenon termed spreading. It
had been attributed to the ability of ParB protein to bridge different segments of DNA, that allows long-distance
interactions. A new way of thinking derived from recent discoveries that ParB protein is not merely a DNA binding
protein but also a novel CTPase enzyme. It was proposed that cytidine triphosphate (CTP) binding to the ParS
and its subsequent hydrolysis cycle drives self-loading of ParS onto parS sites and subsequent sliding away
from the loading sites. However, this “clamp and sliding” model alone has limitations in accounting for in vivo
chromosome immunoprecipitation data. Another critical role of ParB proteins is that they recruit SMC protein
complex to the vicinity of the replication origin. However, little has been known about the SMC protein recruitment
mechanism. Once recruited, bacterial SMC is thought to organize DNAs by actively extruding DNA loops. This
simple mechanism that can explain many aspects of chromosome structuring is required to be demonstrated
with bacterial SMC complex. The PI has almost 15 years of single-molecule techniques expertise and his lab is
devoted to elucidating the mechanisms of various DNA-binding proteins and their impacts on chromosome
structure. During the next five years, the PI’s laboratory will tackle the outstanding problems of underlying ParB
and bacterial SMC working mechanisms and their interplays utilizing his single-molecule approaches and newly
acquired surface plasmon resonance (SPR)-based expertise. Information one could extract from those proteins
in traditional biology approaches is possibly averaged out due to the nature of simultaneous measurements of
multiple proteins (ensemble measurements). Our approach will be expected to uncover hidden mechanisms with
unprecedented details. The in vitro results will be corroborated by in vivo-based assays and theoretical modeling.
The proposed work wi...

## Key facts

- **NIH application ID:** 10277063
- **Project number:** 1R35GM143093-01
- **Recipient organization:** UNIVERSITY OF TEXAS RIO GRANDE VALLEY
- **Principal Investigator:** HYEONGJUN KIM
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $363,386
- **Award type:** 1
- **Project period:** 2021-09-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10277063

## Citation

> US National Institutes of Health, RePORTER application 10277063, Molecular basis of bacterial chromosome segregation and organization (1R35GM143093-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10277063. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
