# Cell cycle regulation and chromosome organization in Caulobacter crescentus

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $303,716

## Abstract

Chromosomes harbor the genetic information thats support life. If fully stretched out, the chromosomal DNA of any organism would be ~1000 times longer than the cell or nucleus that contains it. Thus, chromosomes must be massively compacted. Additionally, chromosomal DNA must be packaged and organized in a manner that enables, and likely facilitates, a range of important cellular processes, including DNA replication, chromosome segregation, transcription, recombination, and repair. Despite the critical and central role of chromosomes in the life of a cell, the mechanisms responsible for their  compaction  and  organization  remain  incompletely defined. Compaction is driven, in part, by DNA supercoiling, which is controlled by a series of topoisomerases. In addition, most organisms encode a suite of DNA-binding proteins that directly shape, compact, and organize genomic DNA. How these proteins structure and organize DNA, and how their activities impact DNA replication, transcription, and chromosome segregation remains  poorly  understood,  particularly  in  bacteria, which do not encode histones. We aim to address this gap in our knowledge, examining the model organism Caulobacter crescentus using a combination of genetic, biochemical, and cell biological assays, along with a set of genome-scale assays, including ChIP-Seq, RNA-Seq, and Hi-C. We will focus on elucidating the in vivo functions and roles of three key chromosome organization components. Specifically, we aim to (i) dissect the in vivo role of SMC (structural maintenance of chromosomes) in establishing the global configuration of the Caulobacter chromosome, (ii) elucidate the mechanisms by which a recently identified  nucleoid-assoicated protein called CnpA affects DNA topology, DNA replication, and transcription, and (iii) identify and characterize the DNA-binding proteins that organize the terminus and promote chromosome segregation. We anticipate that the mechanisms and principles of chromosome organization learned studying Caulobacter  will  be  broadly relevant to other bacteria and, given the universal problem of chromosome compaction, likely to eukaryotes as well. Additionally, because some of the proteins central to compacting bacterial chromosomes, such as topoisomerases, are major antibiotic targets, our work may inform or guide the development of new antibiotics that slow or halt the proliferation of important pathogens.

## Key facts

- **NIH application ID:** 9897555
- **Project number:** 5R01GM082899-13
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Michael Laub
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $303,716
- **Award type:** 5
- **Project period:** 2008-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897555

## Citation

> US National Institutes of Health, RePORTER application 9897555, Cell cycle regulation and chromosome organization in Caulobacter crescentus (5R01GM082899-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9897555. Licensed CC0.

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