High-speed AFM imaging reveals DNA capture and loop extrusion dynamics by cohesin-NIPBL

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dc.citation.articleNumber105296en_US
dc.citation.issueNumber11en_US
dc.citation.journalTitleJournal of Biological Chemistryen_US
dc.citation.volumeNumber299en_US
dc.contributor.authorKaur, Parminderen_US
dc.contributor.authorLu, Xiaotongen_US
dc.contributor.authorXu, Qien_US
dc.contributor.authorIrvin, Elizabeth Marieen_US
dc.contributor.authorPappas, Coletteen_US
dc.contributor.authorZhang, Hongshanen_US
dc.contributor.authorFinkelstein, Ilya J.en_US
dc.contributor.authorShi, Zhubingen_US
dc.contributor.authorTao, Yizhi Janeen_US
dc.contributor.authorYu, Hongtaoen_US
dc.contributor.authorWang, Hongen_US
dc.date.accessioned2024-05-03T15:51:02Zen_US
dc.date.available2024-05-03T15:51:02Zen_US
dc.date.issued2023en_US
dc.description.abstract3D chromatin organization plays a critical role in regulating gene expression, DNA replication, recombination, and repair. While initially discovered for its role in sister chromatid cohesion, emerging evidence suggests that the cohesin complex (SMC1, SMC3, RAD21, and SA1/SA2), facilitated by NIPBL, mediates topologically associating domains and chromatin loops through DNA loop extrusion. However, information on how conformational changes of cohesin-NIPBL drive its loading onto DNA, initiation, and growth of DNA loops is still lacking. In this study, high-speed atomic force microscopy imaging reveals that cohesin-NIPBL captures DNA through arm extension, assisted by feet (shorter protrusions), and followed by transfer of DNA to its lower compartment (SMC heads, RAD21, SA1, and NIPBL). While binding at the lower compartment, arm extension leads to the capture of a second DNA segment and the initiation of a DNA loop that is independent of ATP hydrolysis. The feet are likely contributed by the C-terminal domains of SA1 and NIPBL and can transiently bind to DNA to facilitate the loading of the cohesin complex onto DNA. Furthermore, high-speed atomic force microscopy imaging reveals distinct forward and reverse DNA loop extrusion steps by cohesin-NIPBL. These results advance our understanding of cohesin by establishing direct experimental evidence for a multistep DNA-binding mechanism mediated by dynamic protein conformational changes.en_US
dc.identifier.citationKaur, P., Lu, X., Xu, Q., Irvin, E. M., Pappas, C., Zhang, H., Finkelstein, I. J., Shi, Z., Tao, Y. J., Yu, H., & Wang, H. (2023). High-speed AFM imaging reveals DNA capture and loop extrusion dynamics by cohesin-NIPBL. Journal of Biological Chemistry, 299(11). https://doi.org/10.1016/j.jbc.2023.105296en_US
dc.identifier.digitalPIIS0021925823023244en_US
dc.identifier.doihttps://doi.org/10.1016/j.jbc.2023.105296en_US
dc.identifier.urihttps://hdl.handle.net/1911/115513en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleHigh-speed AFM imaging reveals DNA capture and loop extrusion dynamics by cohesin-NIPBLen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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