The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Growth and Division
Volume 12 - 2024 |
doi: 10.3389/fcell.2024.1420033
S-CDK-regulated bipartite interaction of Mcm10 with MCM is essential for DNA replication
Provisionally accepted
Xueting Wang
1
Lu Liu
2*
Yun Quan
2
Jiaxin Zhang
2*
Huiqiang Lou
2
Yisui Xia
2*
HONGXIANG CHEN
1*
Wenya Hou
2*- 1 Department of Clinical Nutrition, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
- 2 Shenzhen University General Hospital, Shenzhen, China
Mcm10 plays an essential role in activation of replicative helicase CMG through the cell-cycleregulated interaction with the prototype MCM double hexamer in Saccharomyces cerevisiae. In this study, we reported that Mcm10 is phosphorylated by S-CDKs at S66, which enhances Mcm10-MCM association during S phase. S66A single mutation or even deletion of whole N-terminus (a.a. 1-128) only causes mild growth defects. Nevertheless, S66 becomes indispensable in the absence of Mcm10 C-terminus ((a.a. 463-571), the major MCM-binding domain. By using a two-degron strategy to deplete Mcm10 efficiently, we show that mcm10-S66AΔC has a severe defect in proceeding into S phase. Strikingly, both lethality and S phase deficiency can be rescued by artificially tethering mcm10-S66AΔC with MCM. These findings illustrate how Mcm10-MCM association is regulated as a crucial event in DNA replication initiation.
Keywords: Cell Cycle, DNA Replication, Mcm10, Phosphorylation, protein-protein interaction
Received: 19 Apr 2024; Accepted: 27 Aug 2024.
Copyright: © 2024 Wang, Liu, Quan, Zhang, Lou, Xia, CHEN and Hou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lu Liu, Shenzhen University General Hospital, Shenzhen, 518055, China
Jiaxin Zhang, Shenzhen University General Hospital, Shenzhen, 518055, China
Yisui Xia, Shenzhen University General Hospital, Shenzhen, 518055, China
HONGXIANG CHEN, Department of Clinical Nutrition, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
Wenya Hou, Shenzhen University General Hospital, Shenzhen, 518055, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.