Long Patch Base Excision Repair Proceeds via Coordinated Stimulation of the Multienzyme DNA Repair Complex*

Base excision repair, a major repair pathway in mammalian cells, is responsible for correcting DNA base damage and maintaining genomic integrity. Recent reports show that the Rad9-Rad1-Hus1 complex (9-1-1) stimulates enzymes proposed to perform a long patch-base excision repair sub-pathway (LP-BER), including DNA glycosylases, apurinic/apyrimidinic endonuclease 1 (APE1), DNA polymerase β (pol β), flap endonuclease 1 (FEN1), and DNA ligase I (LigI). However, 9-1-1 was found to produce minimal stimulation of FEN1 and LigI in the context of a complete reconstitution of LP-BER. We show here that pol β is a robust stimulator of FEN1 and a moderate stimulator of LigI. Apparently, there is a maximum possible stimulation of these two proteins such that after responding to pol β or another protein in the repair complex, only a small additional response to 9-1-1 is allowed. The 9-1-1 sliding clamp structure must serve primarily to coordinate enzyme actions rather than enhancing rate. Significantly, stimulation by the polymerase involves interaction of primer terminus-bound pol β with FEN1 and LigI. This observation provides compelling evidence that the proposed LP-BER pathway is actually employed in cells. Moreover, this pathway has been proposed to function by sequential enzyme actions in a “hit and run” mechanism. Our results imply that this mechanism is still carried out, but in the context of a multienzyme complex that remains structurally intact during the repair process

Evolution and connectivity influence the persistence and recovery of coral reefs under climate change in the Caribbean, Southwest Pacific, and Coral Triangle

Corals are experiencing unprecedented decline from climate change‐induced mass bleaching events. Dispersal not only contributes to coral reef persistence through demographic rescue but can also hinder or facilitate evolutionary adaptation. Locations of reefs that are likely to survive future warming therefore remain largely unknown, particularly within the context of both ecological and evolutionary processes across complex seascapes that differ in temperature range, strength of connectivity, network size, and other characteristics. Here, we used eco‐evolutionary simulations to examine coral adaptation to warming across reef networks in the Caribbean, the Southwest Pacific, and the Coral Triangle. We assessed the factors associated with coral persistence in multiple reef systems to understand which results are general and which are sensitive to particular geographic contexts. We found that evolution can be critical in preventing extinction and facilitating the long‐term recovery of coral communities in all regions. Furthermore, the strength of immigration to a reef (destination strength) and current sea surface temperature robustly predicted reef persistence across all reef networks and across temperature projections. However, we found higher initial coral cover, slower recovery, and more evolutionary lag in the Coral Triangle, which has a greater number of reefs and more larval settlement than the other regions. We also found the lowest projected future coral cover in the Caribbean. These findings suggest that coral reef persistence depends on ecology, evolution, and habitat network characteristics, and that, under an emissions stabilization scenario (RCP 4.5), recovery may be possible over multiple centuries