AUTHOR=Wang Xueting , Liu Lu , Chen Mengke , Quan Yun , Zhang Jiaxin , Lou Huiqiang , Xia Yisui , Chen Hongxiang , Hou Wenya 

TITLE=S-CDK-regulated bipartite interaction of Mcm10 with MCM is essential for DNA replication

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 12 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2024.1420033

DOI=10.3389/fcell.2024.1420033

ISSN=2296-634X

ABSTRACT=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.