Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA

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The duplication of genetic material is a prerequisite for cellular growth and proliferation. Under optimal growth conditions, when cells strive to grow and divide, DNA replication must be initiated with high frequency. However, under nutrient limiting conditions cells stop initiating DNA replication to ensure cellular integrity. Here, we identify mechanisms responsible for blocking DNA replication initiation under nutrient limitation in Caulobacter crescentus. In this bacterium nutrient limitation results in a strong downregulation of DnaA, the conserved replication initiator protein, which is required for DNA replication in nearly all bacteria. Our data demonstrate that the downregulation of DnaA depends on a reduction in DnaA synthesis in combination with fast degradation by the protease Lon. The changes in DnaA synthesis are mediated by a post-transcriptional mechanism, which adjusts DnaA translation in response to nutrient availability. The constitutively high rate of DnaA degradation then ensures the rapid clearance of the protein following the changes in translation. Our work exemplifies how regulated protein synthesis and fast degradation of key regulatory proteins allow for the precise and dynamic control of important cellular processes in response to environmental changes.

Vyšlo v časopise: Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005342
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005342

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