The Wonders of Flap Endonucleases: Structure, Function, Mechanism and Regulation

摘要: Processing of Okazaki fragments to complete lagging strand DNA synthesis requires coordination among several proteins. RNA primers and synthesised by polymerase α are displaced δ create bifurcated nucleic acid structures known as 5′-flaps. These 5′-flaps removed Flap Endonuclease 1 (FEN), a structure-specific nuclease whose divalent metal ion-dependent phosphodiesterase activity cleaves with exquisite specificity. FENs paradigms for the 5′ superfamily, members perform wide variety roles in metabolism using similar core domain that displays common biochemical properties structural features. A detailed review FEN structure is undertaken show how substrate recognition occurs achieves cleavage at single phosphate diester. proposed double nucleotide unpairing trap (DoNUT) discussed regards has relevance wider superfamily. The homotrimeric proliferating cell nuclear antigen protein (PCNA) coordinates actions polymerase, ligase facilitating hand-off intermediates between each during fragment maturation maximise through-put minimise consequences being released into cellular environment. numerous partner proteins modulate control its action replication also controlled post-translational modification events, all acting concert maintain precise appropriate replication.