Polo-like kinase 1 (Plk1): an Unexpected Player in DNA Replication

The cell cycle plays fundamental roles in many cellular events, such as proliferation, survival and amplification. Deregulation of the cell cycle might lead to abnormal cell growth, which causes cancer or induces cell death through apoptosis. The eukaryotic cell cycle comprises four stages, G1, S, G2 and mitosis. One of the major tasks throughout the cell cycle is to accurately transfer genetic information from parental cells to the next generation. Thus, the two most important stages of the cell cycle are S phase, in which DNA replication occurs, and mitosis, in which the replicated chromosomes are equally segregated into two daughter cells [1].It is well accepted that DNA replication is initiated bi-directionally at specific loci on chromatin, namely the origins of replication. However, how these origins are selected is still not quite clear. The simplest and best understanding of origins of replication is from study of the budding yeast, Saccharomyces cerevisiae. In this organism, replication origins are specified by the autonomous replication sequences (ARS), which are around 100 base pairs and contain a shared 11-base-pair autonomous consensus sequence (ACS). Origin Recognition Complex (ORC) binds directly to ACS to initiate DNA replication. However, even in a simple system such as this, the ACS is not sufficient in itself to predict the origin; the exact location of ACS on the chromosome is also a critical element. Active origins are usually located at intergenic regions, which explains why only 400 out of 12,000 ACS sites are functional in S. cerevisiae [2,3]. On the other hand, the origins of replication of the fission yeast Schizosaccharomyces pombe differ from those of S. cerevisiae. First, the origins are larger in S. Pombe, usually from 500 to 1000 base pairs; second, the origins of fission yeast do not have an ARS-like consensus sequence. However, evidence does show that the origins of replication of S. Pombe are located mostly at intergenic regions of