Association of SNP41, SNP56 and a novel SNP in PDE4D gene with stroke and its subtypes

A genetic link of the carbon metabolism and DNA replication was recently reported for the representative of Gram-negative bacteria, Escherichia coli. Our studies showed that the viability of thermosensitive replication mutants at high temperature can be improved or fully recovered by deleting certain genes of central carbon metabolism (CCM). In order to improve our understanding of this phenomenon, in this study we analyzed the length and nucleoid distribution of suppressed thermosensitive replication mutants. The dysfunctions in the replication machinery generally lead to formation of elongated cells (termed filaments) that originate from an inhibition of cell division dependent on replication-stress, and to abnormal distribution and compaction of nucleoids. The results reported here provide evidence that deletion of the pta and ackA CCM genes significantly reduces observed cell length in the replication mutants dnaA46, dnaB8, dnaE486, dnaG(ts) and dnaN159. A weaker effect was shown in the tktB dnaE486 double mutant. The CCM enzyme dysfunction restored also the nucleoid shape and position in double mutants. The specificity of these effects was confirmed by overexpression of fully functional genes coding for relevant CCM enzymes, which caused the reversion to the initial filamentous and nucleoid phenotypes. These results indicate that CCM mutations can rescue (or reduce) the cell division defects resulting from various replication mutations. We thus suggest that the replication-metabolism connection may serve as a general mechanism affecting DNA duplication at various levels to adjust this process and the cell division to the status of cell physiology.