Title | Smc5/6's multifaceted DNA binding capacities stabilize branched DNA structures. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Chang JT-H, Li S, Beckwitt EC, Than T, Haluska C, Chandanani J, O'Donnell ME, Zhao X, Liu S |
Journal | Nat Commun |
Volume | 13 |
Issue | 1 |
Pagination | 7179 |
Date Published | 2022 Nov 23 |
ISSN | 2041-1723 |
Keywords | Adenosine Triphosphate, Cell Cycle Proteins, DNA Replication, DNA, Single-Stranded, 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 |
Alternate Journal | Nat Commun |
PubMed ID | 36418314 |
PubMed Central ID | PMC9684126 |
Grant List | R01 GM115809 / GM / NIGMS NIH HHS / United States F30 CA275379 / CA / NCI NIH HHS / United States R35 GM145260 / GM / NIGMS NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
Submitted by bel2021 on December 5, 2022 - 11:02am