Smc5/6’s multifaceted DNA binding capacities stabilize branched DNA structures Journal Article

   

Authors:	Chang, J. T. H.; Li, S.; Beckwitt, E. C.; Than, T.; Haluska, C.; Chandanani, J.; O’Donnell, M. E.; Zhao, X.; Liu, S.
Article Title:	Smc5/6’s multifaceted DNA binding capacities stabilize branched DNA structures
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. © 2022, The Author(s).
Journal Title:	Nature Communications
Volume:	13
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2022-11-23
Start Page:	7179
Language:	English
DOI:	10.1038/s41467-022-34928-9
PROVIDER:	scopus
PMCID:	PMC9684126
PUBMED:	36418314
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142427528&doi=10.1038%2fs41467-022-34928-9&partnerID=40&md5=9337ab3c3be2c00e4d176d3beae0e735
Notes:	Article -- Export Date: 1 December 2022 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/200518