In the research field, regulation of DNA replication during the initiation phase is well known while very little is known about regulation of replication during the elongation period. The process of DNA replication is complex, and it is highly regulated by specific factors in the environment. One factor that impacts regulation is the abundance of nutrients in the cell. In the bacterium Bacillus subtilis, replication elongation is inhibited when the cell undergoes amino acid starvation. In the bacterium Escherichia coli, the same effect of amino acid starvation on the cell is observed as well.

In a recent paper, Jessica DeNapoli, Ashley K. Tehranchi, and Jue D. Wang show that both B. subtilis and E. coli, amino acid limitation induces the production of signaling nucleotides called guanosine tetraphosphate (ppGpp) or guanosine pentaphosphate (pppGpp), which altogether is known as (p)ppGpp. Although these nucleotides exist in both bacteria, there is a difference in concentration levels between the two. In B. subtilis, the concentration levels of pppGpp are higher than the concentration levels of ppGpp, and the opposite is true for E. coli. Within these bacterial cells, (p)ppGpp binds to the DNA primase and functions to inhibit the activity of the DNA primase, preventing the process of DNA replication.

In DeNapoli’s article, she showed that amino acid starvation is highly correlated with the reduction of replication elongation rate in E. coli. Furthermore, results indicated that higher concentrations of (p)ppGpp in the cell create a stronger inhibition of replication elongation. In one of the tests, it showed that the presence of (p)ppGpp in the cell is sufficient to decrease the rate of replication elongation in E. coli even in the absence of amino acid starvation. In conclusion, regulation of elongation is a very significant component in these bacteria because it may function to maintain genome integrity, and with the synthesis of (p)ppGpp, it helps to sustain cellular functions in these cells.