Replication-induced protein synthesis and its importance to proteomics.
Replication-induced protein synthesis (RIPS) can occur following the passage of the replisome due to transcription initiated by RNA polymerase in association with: (i) negative supercoiling trailing the replisome / replication fork, (ii) hemimethylation prior to the action of dam methylase, (iii) transient derepression following passage of the replisome/replication fork and prior to renewed synthesis of the repressor gene-product, and (iv) 'sliding clamp' accessory DNA-binding proteins binding to the lagging strand DNA duplex to retard rotational upstream propagation of supercoils. The latter include subunits of DNA polymerase III in Escherichia coli and gp45 in T4 bacteriophage. By far the most convincing evidence for the existence of RIPS comes from the pulse of protein synthesis which follows the passage of the replisome in late T4 bacteriophage, the dynamics of replication in Escherichia coli, recent results from cDNA high-density expression arrays in yeast and the workings of the lac-operon. More circumstantial evidence is provided by 'leaky' or 'aberrant' protein expression in genetic systems where attempts have been made to turn off protein synthesis by molecular means. In higher vertebrates, RIPS may have a potentially important role in explaining the mechanisms by which thymic and peripheral immune self-tolerance is established, either directly through antigen presentation on dendritic cells or through the presentation of peptides derived from T-cells. The latter model is preferred, as young T-cells will have recently divided and will be dying in large numbers near the antigen-presenting dendritic cells in the thymus. The functional utility of RIPS would appear to be linked to both facilitating cellular metabolism and an improved survival during stress. RIPS, as a potentially universal molecular phenomenon, presents proteomics with numerous challenges and opportunities, both technical and commercial.
Humphery-Smith
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The University of Sydney, Centre for Proteome Research and Gene-Product Mapping, National Innovation Centre, Australian Technology Park, Eveleigh. ian@proteome.usyd.edu.au
D000818:Animals; D004261:DNA Replication; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D014176:Protein Biosynthesis