An ATP-like molecule helps bacteria transfer their DNA to ensure survival of the next generation

All organisms must copy and transfer their DNA to the next generation for life to continue. When bacteria reproduce, their chromosome must be copied and then pulled away from their division site so that when the cell separates, each daughter cell gets a copy of the DNA and the chromosome won't get stuck under the division apparatus.

The details of this process have been under intensive study for the past 35 years. A paper published in January 2020 in the journal elife reports a key breakthrough in understanding this complex process. 

In vitro studies of purified proteins from the bacteria Caulobacter crescentus showed for the first time that the nucleoside cytidine triphosphate (CTP) is important in the chromosome transfer process. CTP is a high-energy molecule, similar to the better known ATP (adenosine triphosphate) that provides the energy to drive many processes inside living cells.

The study of C. crescentus was carried out by Adam Jalal, Ngat Tran and Tung B.K. Le of the Department of Molecular Microbiology at the John Innes Centre in Norwich, England. 

Their work focuses on understanding the biochemical processes that occur in the first stages of chromosome segregation. Bacterial chromosome segregation can be difficult to study because of the compact size of the cells and because the DNA replication often goes on at the same time as the chromosome separation, rather than sequentially as in eukaryotes (organisms with a cell nucleus). 

The system responsible for DNA segregation in these bacteria is called ParABS (Par originally standing for partition). It consists of three parts, ParA, an enzyme that catalyzes the formation or decomposition of ATP, ParB, a DNA binding protein and ParS, the site, or sites, where the partition or segregation originates. 

As cell division begins, the ParB protein binds to the ParS sites where the chromosome will segregate. It creates a nucleoprotein complex there which helps to condense and organize the DNA and prepare it for transport into the mother and daughter cells. 

To accomplish this, the ParB has to move along the DNA chain, a process called “spreading.” The focus of this paper by Jalal, Tran and Le is to describe how the ParB protein first binds to the ParS site and then spreads to adjacent DNA. Their unique discovery was to show that the spreading process uses the high-energy molecule CTP. 

The authors describe the ParB as a clamp that can slide along the DNA chain and can open or close to allow the motion. The authors report that when CTP is bound to ParB, ParB slides more easily along DNA. When CTP is hydrolyzed, the authors think it may encourage ParB to unclamp and be recycled back to a ParS site. More work is needed to better understand this process.

“In this work,” they write, “we showed the enhancing effect of CTP on Caulobacter ParB accumulation on DNA and further demonstrated that ParB spreading requires a closed DNA substrate and that a DNA-binding transcriptional regulator can act as a roadblock to attenuate spreading unidirectionally in vitro.”