Replication-induced protein synthesis and its importance to proteomics

Replication-induced protein synthesis (RIPS) can occur following the passag e of the replisome due to transcription initiated by RNA polymerase in asso ciation with: (i) negative supercoiling trailing the replisome/replication fork, (ii) hemimethylation prior to the action of dam methylase, (iii) tran sient 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 du plex to retard rotational upstream propagation of supercoils. The latter in clude subunits of DNA polymerase Ill in Escherichia coli and gp45 in T4 bac teriophage. By far the most convincing evidence for the existence of RIPS c omes from the pulse of protein synthesis which follows the passage of the r eplisome in late T4 bacteriophage, the dynamics of replication in Escherich ia coli, recent results from cDNA high-density expression arrays in yeast a nd the workings of the lac-operon. More circumstantial evidence is provided by 'leaky' or 'aberrant' protein expression in genetic systems where attem pts have been made to turn off protein synthesis by molecular means. In hig her vertebrates, RIPS may have a potentially important role in explaining t he mechanisms by which thymic and peripheral immune self-tolerance is estab lished, 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 dyin g in large numbers near the antigen-presenting dendritic cells in the thymu s. The functional utility of RIPS would appear to be linked to both facilit ating cellular metabolism and an improved survival during stress. RIPS, as a potentially universal molecular phenomenon, presents proteomics with nume rous challenges and opportunities, bath technical and commercial.