Smc5/6's multifaceted DNA binding capacities stabilize branched DNA structures.
| Publication Type | Academic Article |
| Authors | Chang J, Li S, Beckwitt E, Than T, Haluska C, Chandanani J, O'Donnell M, Zhao X, Liu S |
| Journal | Nat Commun |
| Volume | 13 |
| Issue | 1 |
| Pagination | 7179 |
| Date Published | 11/23/2022 |
| ISSN | 2041-1723 |
| Keywords | Cell Cycle Proteins, DNA, Viral |
| Abstract | Smc5/6 is an evolutionarily conserved SMC complex with roles in DNA replication and repair, as well as in viral DNA restriction. Understanding its multiple functions has been hampered by a lack of mechanistic studies on how the Smc5/6 complex associates with different types of DNA. Here we address this question by simultaneously visualizing the behavior of Smc5/6 on three types of DNA, namely double-stranded (ds) DNA, single-stranded (ss) DNA, and junction DNA formed by juxtaposed ss- and dsDNA, using correlative single-molecule fluorescence and force microscopy. We find that Smc5/6 displays distinct behaviors toward different types of DNA, dynamically associating with dsDNA while stably binding to junction DNA. Mechanistically, both the Nse1-3-4 subcomplex and ATP binding enhance the complex's dsDNA association. In contrast, Smc5/6's assembly onto ssDNA emanating from junction DNA, which occurs even in the presence high-affinity ssDNA binders, is aided by Nse1-3-4, but not by ATP. Moreover, we show that Smc5/6 protects junction DNA stability by preventing ssDNA annealing. The multifaceted DNA association behaviors of Smc5/6 provide a framework for understanding its diverse functions in genome maintenance and viral DNA restriction. |
| DOI | 10.1038/s41467-022-34928-9 |
| PubMed ID | 36418314 |
| PubMed Central ID | PMC9684126 |