Table of Contents
Molecular Biology International
Volume 2014, Article ID 574850, 11 pages
http://dx.doi.org/10.1155/2014/574850
Review Article

MCM Paradox: Abundance of Eukaryotic Replicative Helicases and Genomic Integrity

1Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, India
2Department of Zoology, Mahila Mahavidyalaya College, Banaras Hindu University, Varanasi, India
3Department of Radiotherapy & Radiation Medicine, Banaras Hindu University, Varanasi, India

Received 29 August 2014; Accepted 30 September 2014; Published 19 October 2014

Academic Editor: Malayannan B. Subramaniam

Copyright © 2014 Mitali Das et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

As a crucial component of DNA replication licensing system, minichromosome maintenance (MCM) 2–7 complex acts as the eukaryotic DNA replicative helicase. The six related MCM proteins form a heterohexamer and bind with ORC, CDC6, and Cdt1 to form the prereplication complex. Although the MCMs are well known as replicative helicases, their overabundance and distribution patterns on chromatin present a paradox called the “MCM paradox.” Several approaches had been taken to solve the MCM paradox and describe the purpose of excess MCMs distributed beyond the replication origins. Alternative functions of these MCMs rather than a helicase had also been proposed. This review focuses on several models and concepts generated to solve the MCM paradox coinciding with their helicase function and provides insight into the concept that excess MCMs are meant for licensing dormant origins as a backup during replication stress. Finally, we extend our view towards the effect of alteration of MCM level. Though an excess MCM constituent is needed for normal cells to withstand stress, there must be a delineation of the threshold level in normal and malignant cells. This review also outlooks the future prospects to better understand the MCM biology.