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. 2022 May 25;13:2915. doi: 10.1038/s41467-022-30576-1

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 9 — a Schematic illustration of the different stages of DDK recruitment to the MCM2-7 DH and different modes of binding. b DDK bound to the Mcm4. c Cartoon drawing of (b), with missing structural regions extended as dotted lines. DDK forms a lasso around the most N-terminal resolved region of Mcm4. The missing region between Dbf4 motif-M and Dbf4 SCR traps the Mcm4 flexible tail, encircling it at or close to the Cdc7 active site. d DDK is likened to a sewing machine. The main principle being that Mcm4 gets threaded by DDK, and this process allows the kinase to reach the most C-terminal end of the flexible tail. e Simplified version of (c) showing a step-wise hypothetical mechanism of Mcm4 substrate localisation and processive phosphorylation. The region labelled 1, features a part of Dbf4 SCR which forms a hook (lasso) around the rigid surface of Mcm4. The region labelled 2, features an encircled Mcm4 flexible tail that gets threaded through the kinase. The missing structural regions are represented as dotted lines and resolved regions as solid lines.