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- W4293368072 abstract "Abstract DNA replication is highly regulated and primarily controlled at the step of initiation. In bacteria, the replication initiator DnaA and the origin of replication oriC are the primary targets of regulation. Perturbations that increase or decrease replication initiation can cause a decrease in cell fitness. We found that multiple mechanisms, including an increase in replication elongation and a decrease in replication initiation, can compensate for lethal over‐initiation. We found that in Bacillus subtilis , under conditions of rapid growth, loss of yabA , a negative regulator of replication initiation, caused a synthetic lethal phenotype when combined with the dnaA1 mutation that also causes replication over‐initiation. We isolated several classes of suppressors that restored viability to dnaA1 ∆yabA double mutants. Some suppressors ( relA , nrdR ) stimulated replication elongation. Others ( dnaC , cshA ) caused a decrease in replication initiation. One class of suppressors decreased replication initiation in the dnaA1 ∆yabA mutant by causing a decrease in the amount of the replicative helicase, DnaC. We found that decreased levels of helicase in otherwise wild‐type cells were sufficient to decrease replication initiation during rapid growth, indicating that the replicative helicase is limiting for replication initiation. Our results highlight the multiple mechanisms cells use to regulate DNA replication." @default.
- W4293368072 created "2022-08-28" @default.
- W4293368072 creator A5056293755 @default.
- W4293368072 creator A5077820135 @default.
- W4293368072 creator A5083355596 @default.
- W4293368072 date "2022-09-11" @default.
- W4293368072 modified "2023-10-14" @default.
- W4293368072 title "Multiple mechanisms for overcoming lethal over‐initiation of <scp>DNA</scp> replication" @default.
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- W4293368072 doi "https://doi.org/10.1111/mmi.14976" @default.
- W4293368072 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36053906" @default.
- W4293368072 hasPublicationYear "2022" @default.