Structural highlights
Function
SMC5_YEAST Acts in a DNA repair pathway for removal of UV-induced DNA damage that is distinct from classical nucleotide excision repair and in repair of ionizing radiation damage. Functions in homologous recombination repair of DNA double strand breaks and in recovery of stalled replication forks.
Publication Abstract from PubMed
The Smc5/6 complex plays an essential role in the resolution of recombination intermediates formed during mitosis or meiosis, or as a result of the cellular response to replication stress. It also functions as a restriction factor preventing viral replication. Here, we report the cryogenic EM (cryo-EM) structure of the six-subunit budding yeast Smc5/6 holo-complex, reconstituted from recombinant proteins expressed in insect cells - providing both an architectural overview of the entire complex and an understanding of how the Nse1/3/4 subcomplex binds to the hetero-dimeric SMC protein core. In addition, we demonstrate that a region within the head domain of Smc5, equivalent to the 'W-loop' of Smc4 or 'F-loop' of Smc1, mediates an important interaction with Nse1. Notably, mutations that alter the surface-charge profile of the region of Nse1 which accepts the Smc5-loop, lead to a slow-growth phenotype and a global reduction in the chromatin-associated fraction of the Smc5/6 complex, as judged by single molecule localisation microscopy experiments in live yeast. Moreover, when taken together, our data indicates functional equivalence between the structurally unrelated KITE and HAWK accessory subunits associated with SMC complexes.
Cryo-EM structure of the Smc5/6 holo-complex.,Hallett ST, Campbell Harry I, Schellenberger P, Zhou L, Cronin NB, Baxter J, Etheridge TJ, Murray JM, Oliver AW Nucleic Acids Res. 2022 Aug 22. pii: 6673127. doi: 10.1093/nar/gkac692. PMID:35993814[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hallett ST, Campbell Harry I, Schellenberger P, Zhou L, Cronin NB, Baxter J, Etheridge TJ, Murray JM, Oliver AW. Cryo-EM structure of the Smc5/6 holo-complex. Nucleic Acids Res. 2022 Aug 22. pii: 6673127. doi: 10.1093/nar/gkac692. PMID:35993814 doi:http://dx.doi.org/10.1093/nar/gkac692
