Replication Proteins and Human Disease

In this article, we discuss the significance of DNA replication proteins in human disease. There is a broad range of mutations in genes encoding replication proteins, which result in several distinct clinical disorders that share common themes. One group of replication proteins, the MCMs, has emerged as effective biomarkers for early detection of a range of common cancers. They offer practical and theoretical advantages over other replication proteins and have been developed for widespread clinical use.Semiconservative replication of DNA is essential for cellular proliferation. Therefore, mutation of genes encoding the replication machinery could be thought to be fundamentally harmful to an organism. However, inherited and acquired mutations in such genes do occur, resulting in a broad spectrum of disease. The first half of this article outlines the phenotypes associated with several classes of replication disorders, before focusing on the pre-replicative complex (pre-RC) and its involvement in both inherited and acquired human disease. In the second half, we discuss the utility of replication proteins as oncological disease markers, again with emphasis on pre-RC components. The function and mechanism of action of the replication proteins described here are covered in depth in other articles in this collection (Holt and Reyes 2012; Bell and Botchan 2013; Siddiqui et al. 2013).