Integrative analysis reveals unique structural and functional features of the Smc5/6 complex Journal Article
| Authors: | Yu, Y.; Li, S.; Ser, Z.; Sanyal, T.; Choi, K.; Wan, B.; Kuang, H.; Sali, A.; Kentsis, A.; Patel, D. J.; Zhao, X. |
| Article Title: | Integrative analysis reveals unique structural and functional features of the Smc5/6 complex |
| Abstract: | Structural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for the distinct functions of Smc5/6 is poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/ 6 holo-complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that the Smc5/6 complex possesses several unique features, while sharing some architectural characteristics with other SMC complexes. In contrast to arm-folded structures of cohesin and condensin, Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5/Nse6 subcomplex, with the latter also serving as a linchpin connecting distal parts of the complex. Our 3.0-Å resolution cryoelectron microscopy structure of the Nse5/Nse6 core further reveals a clasped-hand topology and a dimeric interface important for cell growth. Finally, we provide evidence that Nse5/Nse6 uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative study identifies distinct structural features of the Smc5/6 complex and functional cooperation among its coevolved unique subunits. © 2021 National Academy of Sciences. All rights reserved. |
| Keywords: | sumoylation; smc5/6 complex; nse5; nse6; structural maintenance of chromosomes |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 118 |
| Issue: | 19 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2021-05-11 |
| Start Page: | e2026844118 |
| Language: | English |
| DOI: | 10.1073/pnas.2026844118 |
| PUBMED: | 33941673 |
| PROVIDER: | scopus |
| PMCID: | PMC8126833 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2021 -- Source: Scopus |
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