FtsZ phosphorylation brings about growth arrest upon DNA damage in Deinococcus radiodurans

Abstract

The polymerization/depolymerization dynamics of FtsZ play a pivotal role in cell division in the majority of the bacteria. Deinococcus radiodurans, a radiationresistant bacterium, shows an arrest of growth in response to DNA damage with no change in the level of FtsZ. This bacterium does not deploy LexA/RecA type of DNA damage response and cell cycle regulation, and its genome does not encode SulA homologues of Escherichia coli, which attenuate FtsZ functions in response to DNA damage in other bacteria. A radiation-responsive Ser/Thr quinoprotein kinase (RqkA), characterized for its role in radiation resistance in this bacterium, could phosphorylate several cognate proteins, including FtsZ (drFtsZ) at Serine 235 (S235) and Serine 335 (S335) residues. Here, we reported the detailed characterization of S235 and S335 phosphorylation effects in the regulation of drFtsZ functions and demonstrated that the phospho-mimetic replacements of these residues in drFtsZ had grossly affected its functions that could result in cell cycle arrest in response to DNA damage in D. radiodurans. Interestingly, the phospho-ablative replacements were found to be nearly similar to drFtsZ, whereas the phospho-mimetic mutant lost the wild-type protein's signature characteristics, including its dynamics under normal conditions. The kinetics of post-bleaching recovery for drFtsZ and phospho-mimetic mutant were nearly similar at 2 h post-irradiation recovery but were found to be different under normal conditions. These results highlighted the role of S/T phosphorylation in the regulation of drFtsZ functions and cell cycle arrest in response to DNA damage, which is demonstrated for the first time, in any bacteria.

DivIVA Phosphorylation Affects Its Dynamics and Cell Cycle in Radioresistant Deinococcus radiodurans

“…Nevertheless, a DNA damage-responsive Ser/Thr quinoprotein kinase (RqkA) phosphorylates both DNA repair and cell division proteins in this bacterium ( 29 , 39 ). Interestingly, phosphorylation of DNA repair proteins enhances their activity while negatively affecting the functions of the cell division proteins, such as FtsZ, in vitro ( 40 , 51 ).…”

DNA damage response and cell cycle regulation in bacteria: a twist around the paradigm

“…Similarly, FtsZ phosphorylation has also affected the functional interaction of FtsZ with FtsA as well as the polymerization dynamics of FtsZ in vitro . Cells expressing phosphor-mimetic mutants of FtsZ behaved differently than cells expressing phosphor-ablative and wild type, indicating the arrest of FtsZ function upon phosphorylation by RqkA ( Chaudhary et al, 2023a ). Furthermore, DivIVA phosphorylation at the T19 site had altered its typical pattern of localization near the new septum site and completely distorted its ability to determine the plane of the next division that is normally perpendicular to the previous plane of cell division ( Chaudhary et al, 2023b ) The enhancement of DNA repair function with the concurrent arrest of cell division upon Ser/Thr phosphorylation by RqkA nearly mimics these processes upon DNA damage as observed in eukaryotes ( Sancar et al, 2004 ).…”

Complete genome sequence of Deinococcus rubellus Ant6 isolated from the fish muscle in the Antarctic Ocean

“…Deinococcus have also been reported to stop cell division in response to radiation stress; however, the exact mechanism of cell division arrest is not yet fully understood. Recent studies suggested that the phosphorylation of key cell division proteins such as FtsZ or DivIVA by the Serine/Threonine protein kinases (STPKs) (e.g., RqkA) could result in cell cycle arrest under radiation stress in D. radiodurans ( Chaudhary et al, 2023a ; Chaudhary et al, 2023b ). Importantly, both the Deinococcus strain (Ant6 and R1) contains large number of STPK but these proteins were not detected in the radioresistance strain K12 ( Supplementary Table S7 ).…”