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

ABSTRACT: In Escherichia coli, membrane stress due to interrupted lipoprotein (Lpp) maturation impairs DNA replication and arrests cell growth. How Lpp maturation and DNA replication are connected remains unclear. We demonstrate that upon membrane stress, the Rcs stress-response pathway is activated, and the replication initiator DnaA is lost, which explains the replication block. However, Lon protease, a key regulator of the Rcs pathway, is not required for the DnaA loss. We further ruled out the involvement of (p)ppGpp, one of the major mediators of stress responses in bacteria. On the other hand, upon deletion of the ClpP protease gene, DnaA was stable, replication was not inhibited, and there was no cell-growth arrest. In wild-type cells, overexpression of DnaA was lethal even without the

SUBMITTER: Gbolahan A 

PROVIDER: S-EPMC12288453 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature