Insights into the MCM functional mechanism: lessons learned from the archaeal MCM complex

Abstract

The helicase function of the minichromosome maintenance protein (MCM) is essential for genomic DNA replication in archaea and eukaryotes. There has been rapid progress in studies of the structure and function of MCM proteins from different organisms, leading to better understanding of the MCM helicase mechanism. Because there are a number of excellent reviews on this topic, we will use this review to summarize some of the recent progress, with particular focus on the structural aspects of MCM and their implications for helicase function. Given the hexameric and double hexameric architecture observed by X-ray crystallography and electron microscopy of MCMs from archaeal and eukaryotic cells, we summarize and discuss possible unwinding modes by either a hexameric or a double hexameric helicase. Additionally, our recent crystal structure of a full length archaeal MCM has provided structural information on an intact, multi-domain MCM protein, which includes the salient features of four unusual β-hairpins from each monomer, and the side channels of a hexamer/double hexamer. These new structural data enable a closer examination of the structural basis of the unwinding mechanisms by MCM.

Keywords::

• DNA replication
• replicative helicase
• nucleic-acid motor
• β-hairpin
• AAA+ initiator protein

Acknowledgements

We thank Lauren Holden for her assistance in editing the manuscript, and Drs. D. Gai and B. Greenleaf for insightful discussions.

Declaration of interest

This work is supported in part by NIH grant R01GM080338 to XC. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Editor: Michael M. Cox