Do stalled replication forks synthesize a specific alarmone?
Potential causes of premature arrest of a replication fork in vivo include an encounter with a chemical lesion in the DNA, inhibition of one of the essential enzymes of the fork, and spontaneous failure of the fork due to its finite degree of processivity. I suggest that a premature arrest of either a eukaryotic or prokaryotic replication fork induces it to enter a different state in which the fork synthesizes a specific signal nucleotide ("alarmone"). One function of the postulated new alarmone would be to increase the probability of re-initiation of DNA replication, either in cis (at an origin proximal to a site of the fork arrest) or in trans (at many different origins). An additional, mechanistically related function of the postulated alarmone could be to increase the probability of re-assembly of an arrested fork beyond an otherwise impassable DNA lesion. In case of multiple fork arrests, an alarmone-mediated increase in the probability of replicon reinitiation (disproportionate DNA replication) would result in gene amplification at many different loci, thereby increasing the probability of cell's survival in a cytotoxic medium. Other likely functions of a fork-produced alarmone may include stimulation of DNA repair pathways including excision repair.(ABSTRACT TRUNCATED AT 250 WORDS)
D000227:Adenine Nucleotides / Q000096:biosynthesis*; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D000818:Animals; D004257:DNA Polymerase II / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D005784:Gene Amplification
D000227:Adenine Nucleotides; D004257:DNA Polymerase II; D000604:Amino Acyl-tRNA Synthetases