Structural basis for oligomerization of the eukaryotic replication factor Mcm10.

摘要

This work examines the role of the N-terminal domain (NTD) in Mcm10 structure and self-assembly. Specifically, NTD was identified to be responsible for full-length xMcm10 oligomerization. The structure of the coiled-coil motif within NTD was determined to be a homotrimer by X-ray crystallography. Both dimer and trimer were observed in solution by AUC. Mutations of the interacting residues within NTD disrupted oligomerization of NTD, as well as full-length Mcm10. A dimer/trimer coiled coil conversion model was proposed. This study puts us one step further in understanding Mcm10 oligomerization, and thus its role in DNA replication initiation. Future studies to better characterize the coordination of ID and CTD in DNA binding, the complex structure of FL Mcm10 and its interacting partners, and the investigation of the functional significance of Mcm10 will help us better understand Mcm10 and DNA replication. This research will shed light on drug discovery and treatment of DNA-replication related diseases, including cancer.