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DNA repair

Stabilization of DNA fork junctions by Smc5/6 complexes


A team led by Johannes Stigler provides a model for the complex-mediated recognition of replication stress or DNA lesions

stigler-cellrep22_graphabstractSMC 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.

Original Publication:

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,