Ribosomal vs Non-ribosomal peptide synthesis:

• Oxytocin is encoded by the OXT gene and translated ribosomally as a preprohormone.
• Gramicidin S is a cyclic decapeptide antibiotic synthesized independently of ribosomes and mRNA templates by multienzyme non-ribosomal peptide synthetases (NRPS).
• Insulin is gene-encoded and synthesized ribosomally on the rough endoplasmic reticulum as preproinsulin.
• Actinomycin D contains non-protein amino acids and is assembled non-ribosomally by NRPS complexes in Streptomyces.

Enzymatic activities of E. coli DNA polymerase I:

• DNA Pol I has $3'\to 5'$ exonuclease activity that proofreads newly incorporated nucleotides.
• It possesses unique $5'\to 3'$ exonuclease activity that removes RNA primers ahead of the growing chain.
• Combining $5'\to 3'$ exonuclease degradation with simultaneous $5'\to 3'$ DNA polymerization enables DNA Pol I to carry out nick translation.
• DNA ligation is specifically performed by DNA ligase to seal the remaining phosphodiester backbone nick, not by DNA Pol I.

Significance of Okazaki's experiments:

• Continuous synthesis describes leading strand synthesis only.
• The semiconservative mode of DNA replication was proven by Matthew Meselson and Franklin Stahl (1958).
• The dispersive model was disproved by Meselson and Stahl.
• Reiji and Tsuneko Okazaki demonstrated that because DNA polymerases synthesize DNA exclusively in the $5'\to 3'$ direction, replication at the fork proceeds semi-discontinuously: continuously on the leading strand and discontinuously via Okazaki fragments on the lagging strand.