A team led by Johannes Stigler provides a model for the complex-mediated recognition of replication stress or DNA lesions
SMC complexes play key roles in genome maintenance, where they ensure efficient genome replication and segregation. The SMC complex Smc5/6 is a crucial player in DNA replication and repair, yet many molecular features that determine its roles are unclear. Johannes Stigler and his team use single-molecule microscopy to investigate Smc5/ 6’s interaction with DNA. They find that Smc5/6 forms oligomers that dynamically redistribute on dsDNA by 1D diffusion and statically bind to ssDNA. Using combined force manipulation and single-molecule microscopy, they generate ssDNA-dsDNA junctions that mimic structures present in DNA repair intermediates or replication forks. They show that Smc5/6 accumulates at these junction sites, stabilizes the fork, and promotes the retention of RPA. Their observations provide a model for the complex’s enrichment at sites of replication stress and DNA lesions from where it coordinates the recruitment and activation of downstream repair proteins.
Stabilization of DNA fork junctions by Smc5/6 complexes revealed by single-molecule imaging
Tanasie N-L, Gutierrez-Escribano P, Jaklin S, Aragon L and Stigler J
Cell Rep. 2022, https://doi.org/10.1016/j.celrep.2022.111778