Fig. 6: A model illustrating dynamic interactions at replication origins during the recovery from replication stress.
From: Selective interactions at pre-replication complexes categorize baseline and dormant origins
Left, in cells harboring WT-RecQL4, recruitment of the Treslin-MTBP complex marks a sub-group of baseline origins (e.g. origin 1) whereas pRecQL4-S89 (pRecQL4) associates with dormant origins (e.g. origin 2). When cells encounter replication stress, baseline origins can stall (red halo) but dormant origins, which do not initiate replication, are not affected and still maintain MCM complexes (green ring). Although pRecQL4 binding does not allow initiation from dormant origins under normal circumstances (see Fig. 2F), RecQL4 dissociates from origins when cells recover from replication stress and allows MTBP re-association with those origins. Upon the binding of MTBP and Treslin to dormant origins, these origins initiate replication to complete DNA synthesis. Right, in cells that do not harbor pRecQL4-S89 (either RecQL4 depleted or harboring the RecQL4-S89A substitution), MTBP and Treslin associate with both origins 1 and 2, and replication initiates from both origins as cells encounter acute replication stress. Under these conditions, replication from dormant origins cannot rescue the damage after replication stress is removed, preventing normal recovery and leading to the accumulation of ssDNA and subsequent DNA damage.
