Foreword: Eukaryotic DNA replication: is time of the essence?
The visionary studies of Watson and Crick (1953) first proposed a structure for DNA to suggest a ‘possible copying mechanism for the genetic material’. Ever since, cell biologists have marvelled at the mysteries by which this most fundamental process of cell proliferation is controlled. The importance of mechanisms that regulate DNA synthesis is selfevident, given the biological imperative to maintain genetic integrity from one cell generation to the next. Moreover, in order to preserve the genetic information, it is essential that synthesis is performed with absolute precision, as any errors might generate chromosomal defects, which can ultimately lead to cell transformation or death. As is often the case in biology, our desire to understand how a synthetic process might fail demands a molecular understanding of that process under normal conditions. In eukaryotes, a molecular description of the replication machinery and basic mechanisms that regulate synthesis have been developed using biochemical analysis of yeast (Waga and Stillman 1998) and Xenopus (Chong et al. 1995) extracts as model systems. These studies have elaborated the key components of the synthetic machinery, the make-up of the origin recognition complex that defines where synthesis can begin and the role of the MCM2-7 complex that acts to ‘license’ DNA for replication and ensure that each potential origin is only able to operate once per cell cycle. At this level, essentially, the same basic machinery is used throughout eukaryotes. However, while this basic synthetic machinery is now well characterised, many of the mechanisms that control the synthetic process remain enigmatic. This is particularly evident in higher eukaryotes, where increasing organismal complexity and associated increases in genome size place huge demands on the need to perform replication with absolute precision. In higher eukaryotes, epigenetic histone modifications that fix patterns of gene expression during cell specialisation must also be recapitulated during DNA synthesis. Perhaps as part of this process, the mammalian S phase is known to be organised in time so that gene-rich chromosomal R-bands are replicated early in S phase before synthesis of the gene-poor G-bands can begin (Drouin et al. 1994). Put in these simplistic terms, it is easy to see why a temporally structure S phase programme must be a fundamental feature of the eukaryotic S phase. Yet, despite this Chromosome Research (2010) 18:1–5 DOI 10.1007/s10577-009-9106-2