The Rtt107 BRCT scaffold and its partner modification enzymes collaborate to promote replication

Faithful duplication of the entire genome during each cell cycle is key for genome maintenance. Each stage of DNA replication, including initiation, progression, and termination, is tightly regulated. Some of these regulations enable replisomes to overcome tens of thousands of template obstacles that block DNA synthesis. Previous studies have identified a large number of proteins that are dedicated to this mission, including protein modification enzymes and scaffold proteins. Protein modification enzymes can bestow fast and reversible changes on many substrates, and thus are ideal for coordinating multiple events needed to promptly overcome replication impediments. Scaffold proteins can support specific protein-protein interactions that enable protein complex formation, protein recruitment, and partner enzyme functions. Taken together with previous studies, our recent work elucidates that a group of modification and scaffold proteins form several complexes to aid replication progression and are particularly important for synthesizing large replicons. Additionally, our work reveals that the intrinsic plasticity of the replication initiation program can be used to compensate for deficient replication progression.