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PubMed · 6672476

Do stalled replication forks synthesize a specific alarmone?

A Varshavsky
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Abstract

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)

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Adenine NucleotidesAmino Acyl-tRNA SynthetasesAnimalsDNA Polymerase IIDNA RepairDNA ReplicationGene AmplificationJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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A Varshavsky. 1983-12-21. Do stalled replication forks synthesize a specific alarmone?. https://doi.org/10.1016/0022-5193(83)90228-x

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