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

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dc.citation.articleNumber105296
dc.citation.issueNumber11
dc.citation.journalTitleJournal of Biological Chemistry
dc.citation.volumeNumber299
dc.contributor.authorKaur, Parminder
dc.contributor.authorLu, Xiaotong
dc.contributor.authorXu, Qi
dc.contributor.authorIrvin, Elizabeth Marie
dc.contributor.authorPappas, Colette
dc.contributor.authorZhang, Hongshan
dc.contributor.authorFinkelstein, Ilya J.
dc.contributor.authorShi, Zhubing
dc.contributor.authorTao, Yizhi Jane
dc.contributor.authorYu, Hongtao
dc.contributor.authorWang, Hong
dc.date.accessioned2024-05-03T15:51:02Z
dc.date.available2024-05-03T15:51:02Z
dc.date.issued2023
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.
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.2023.105296
dc.identifier.digitalPIIS0021925823023244
dc.identifier.doihttps://doi.org/10.1016/j.jbc.2023.105296
dc.identifier.urihttps://hdl.handle.net/1911/115513
dc.language.isoeng
dc.publisherElsevier
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.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleHigh-speed AFM imaging reveals DNA capture and loop extrusion dynamics by cohesin-NIPBL
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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