Figure 8.

Postreplicative gap-filling on a leading strand template. An unrepaired UV-induced lesion ( ) encountered in a leading strand template leads to stalling of the replication fork downstream of the lesion (as depicted in Figure 5). In postreplicative gap-filling, bypass of the UV-induced lesion occurs after the replication fork has been re-started through a re-priming event, as follows. 1) PrimPol is recruited to the RPA-coated ssDNA downstream of a UV-induced lesion by a direct interaction with RPA. Once localized, PrimPol synthesizes a nascent primer at a random location downstream of the offending damage and a new PCNA ring is loaded onto the nascent 3′ hydroxyl terminus. This leaves behind an RPA-coated ssDNA gap (postreplicative gap) containing PCNA and the lesion. 2) Pol δ faithfully extends the nascent primer terminus to the stalled CMG helicase where 3) the bound pol ε rapidly replaces pol δ on the leading strand template, re-starting progression of the stalled replication fork. 4) Eventually, the offending DNA lesion within the postreplicative gap (shown) is bypassed by one or more TLS pols, extending the aborted primer terminus to an undamaged section of the leading strand template. 5) Pol δ “fills in” the remainder of the postreplicative gap and the 5′ RNA end of the downstream duplex region is removed as in Okazaki fragment processing/metabolism³. 6) The resident PCNA is removed some time after the fully-extended primer terminus is ligated to the 5′ end of the downstream daughter DNA.