Replication Disruption: Mechanisms and Consequences in Woeseiales

Replication disruption, from energy lack or cellular damage, can cause replication fork collapse leading to DNA damage and cell death [85]. The five isolates, including W. oceani XK5T and most Woeseiales, possess GTP pyrophosphokinase (relA) and GTP diphosphokinase/guanosine-3',5'-bis(diphosphate) 3'-diphosphatase (spoT) (Fig. 5). During nutrient limitation, relA produces guanosine pentaphosphate and tetraphosphate ((p)ppGpp), which inhibit protein biosynthesis and DNA replication through RNA polymerase binding [86]. SpoT activates in response to nutrient limitation or environmental stress and regulates (p)ppGpp accumulation [87]. Additionally, the five isolates and W. oceani XK5T genomes, along with most Woeseiales MAGs, encode the protease Lon (Fig. 5), which degrades DnaA in the global protein-folding state caused by perturbation, thereby inhibiting DNA replication [88].