ClpAP is an auxiliary protease for DnaA degradation in Caulobacter crescentus. Issue 6 (17th October 2016)

• Record Type: Journal Article
• Authors: Liu, Jing; Francis, Laura I.; Jonas, Kristina; Laub, Michael T.; Chien, Peter
• Is Part Of: Molecular microbiology. Volume 102:Issue 6(2016)
• Page Start: 1075
• Page End: 1085
• Publication Date: 2016-10-17
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13537
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: The Clp family of proteases is responsible for controlling both stress responses and normal growth. In Caulobacter crescentus, the ClpXP protease is essential and drives cell cycle progression through adaptor‐mediated degradation. By contrast, the physiological role for the ClpAP protease is less well understood with only minor growth defects previously reported for ΔclpA cells. Here, we show that ClpAP plays an important role in controlling chromosome content and cell fitness during extended growth. Cells lacking ClpA accumulate aberrant numbers of chromosomes upon prolonged growth suggesting a defect in replication control. Levels of the replication initiator DnaA are elevated in ΔclpA cells and degradation of DnaA is more rapid in cells lacking the ClpA inhibitor ClpS. Consistent with this observation, ClpAP degrades DnaA in vitro while ClpS inhibits this degradation. In cells lacking Lon, the protease previously shown to degrade DnaA in Caulobacter, ClpA overexpression rescues defects in fitness and restores degradation of DnaA. Finally, we show that cells lacking ClpA are particularly sensitive to inappropriate increases in DnaA activity. Our work demonstrates an unexpected effect of ClpAP in directly regulating replication through degradation of DnaA and expands the functional role of ClpAP in Caulobacter . Abstract : In Caulobacter crescentus, levels of the replication initiator protein DnaA are known to be controlled through proteolysis by the Lon protease. In this work, we show that the ClpAP protease also contributes to DnaA degradation in a process inhibited by the ClpS adaptor. ClpAP degrading DnaA is particularly important during extended growth and entry into the stationary phase. Having two proteolytic pathways controlling an essential replication factor is an excellent strategy to ensure robust control under different growth conditions.