Principal Investigator Alan Grossman
Just as cells sense internal and external conditions and modulate transcription, they also modulate replication, both initiation and elongation of replication. Sudden decreases in nutrient availability cause a relatively rapid inhibition in replication elongation. We monitored the progression of replication forks using DNA microarrays and found that the inhibition in elongation of replication caused by nutritional downshift is due to accumulation of the signaling molecules pppGpp and ppGpp. We showed that these signaling nucleotides inhibit primase, an essential component of the replication machinery. This regulation is likely to prevent DNA damage or mutagenesis that could occur during replication in the absence of sufficient dNTPs and provides a link between nutrient availability and the preservation of genome integrity, likely forming part of a general bacterial stress response to enhance survival in adverse conditions.