RESEARCH HIGHLIGHTS BACTERIAL PHYSIOLOGY Abracadabra! Replication shutdown DOI: 10.1038/nrmicro1666 When bacteria are starved, the at specific left and right stringent revealed that (p)ppGpp targets DNA stringent response coordinates cell termination (ter) sites located either primase, an RNA polymerase that is URLs functions to divert scarce resources side of the ori. dedicated to priming DNA replica- Bacillus subtilis from growth and cell division to In the latest report, Wang et al. tion. Just where (p)ppGpp binds to http://www.ncbi.nlm.nih.gov/ entrez/query.fcgi?db=genome amino-acid biosynthesis in order to used time-resolved whole genome DNA primase is not yet known but prj&cmd=Retrieve&dopt=Over aid survival. Publishing in Cell, Wang microarrays to monitor the movement the mechanism of inhibition is sensi- view&list_uids=17579 et al. now show that the stringent of replication forks in synchronized tive, because gradually increasing Escherichia coli response shuts down genome replica- cell cultures by pinpointing the dou- (p)ppGpp concentrations switches http://www.ncbi.nlm.nih.gov/ tion in Bacillus subtilis and conclude bling of DNA content at individual off elongation in a dose-dependent entrez/query.fcgi?db=genome prj&cmd=Retrieve&dopt=Over that signals deployed during the gene loci. When B. subtilis cells were fashion. The response can therefore view&list_uids=12319 stringent response directly inhibit starved, replication forks stalled at the be tuned according to the extent of DNA primase, an essential part of the ter sites in accordance with previous nutrient limitation. DNA replication machinery. findings. But replication forks also This study provides an elegant The stringent response is mediated stalled within minutes — independ- link between nutrient availability and by the small guanosine nucleotides ent of their location — when an the preservation of genome integrity (p)ppGpp — ppGpp and pppGpp asynchronous population was starved. and might form part of a general — that are collectively known as alar- This argues against the presence of bacterial stress response to ensure mones or magic spots. Upon binding dedicated cis-acting sites at which survival in adverse conditions. to the RNA polymerase, (p)ppGpp elongation can be terminated. Susan Jones inhibits the transcription of genes that RecA is usually recruited to repair ORIGINAL RESEARCH PAPER Wang, J. D., encode the translation machinery and chromosomes when replication Sanders, G. M. & Grossman, A. D. Nutritional promotes the transcription of genes forks stall in bacteria, but the authors control of elongation of DNA replication by (p)ppGpp. Cell 128, 865–875 (2007) that encode amino-acid biosynthetic found that this did not happen in the pathways. In Escherichia coli the strin- stringent response of B. subitilis. In gent response also inhibits the initia- fact, the authors showed that stalled tion of genome replication, thereby forks can restart replication when shifting the focus of cellular activity nutrients become available, and from cell division to cell survival. argue that rapidly stalling replication In 1991, work from Simone prevents the accumulation of double- Séror’s laboratory first demonstrated strand breaks that might arise from that, in B. subtilis, the stringent genome replication in the absence of response regulates replication elonga- sufficient dNTPs. tion rather than initiation. Unlike the The authors sought to probe mechanisms underlying the initiation how starvation and chromosome of DNA replication in bacteria, those replication are coordinated. The controlling elongation of replication obvious candidate was the replica- are not well understood. Replication tion termination (Rtp) protein, but of the lone circular B. subtilis chro- replication forks stalled in response mosome initiates from a single origin to starvation in a mutant that lacked of replication (ori) and proceeds Rtp. A mutant lacking RelA, which bidirectionally around the chromo- is a (p)ppGpp synthetase that is acti- some. Subsequent work revealed vated in the stringent response, did that starvation results in an abrupt not terminate replication when cells shutdown of chromosome replication were starved. A suite of experiments NATURE REVIEWS | MICROBIOLOGY VOLUME 5 | MAY 2007 © 2007 Nature Publishing Group .