A novel membrane stress response that blocks chromosomal replication by targeting the DnaA initiator via the ClpP protease

The observation that DNA replication stress can block cell division in <i>E. coli</i> (SOS response) introduced the concept of checkpoint control in the cell cycle. Here, we describe a novel checkpoint control that functions in the opposite direction: membrane stress causing replication block. We show how the accumulation of precursor lipoprotein (pLpp) could block replication. The pLpp accumulation causes a response culminating in activating the ClpP protease that blocks replication by targeting the initiator DnaA. DnaA being vital and highly conserved, a detailed understanding of the response pathway is likely to open new avenues to treat bacterial infection.