Only those exacting editors at Cell could seriously ask you to review the past century of cell cycle research and to predict the course of research for the next century, and to do it all in 10 pages! It is unrealistic to try to be comprehensive in such a review, and so I will focus on what I consider to be the important principles underlying the cell cycle, with less emphasis on detailed descriptions of molecular mechanisms which would degenerate into lists of genes and proteins. Referencing will be minimal, and will be restricted to reviews, a few key primary publications, and to books written in English for summaries of the earlier literature.

Let us begin at the end of the century by summarizing what is now known about the cell cycle. We know that the cell cycle is the universal process by which cells reproduce, and that it underlies the growth and development of all living organisms. The most important events of the cell cycle are those concerned with the copying and partitioning of the hereditary material, that is replicating the chromosomal DNA during S phase and separating the replicated chromosomes during mitosis. Controls operate that regulate onset of these events and compensate for errors in their execution. The molecular basis of these controls is highly conserved from simple unicellular eukaryotes such as yeast to complex metazoans such as ourselves. The precision with which cell cycle events are executed ensures the survival of living organisms, while loss of this precision increases genomic instability, an important factor in the formation of cancer. The mitotic cell cycle is modified to a meiotic cycle during gamete formation, leading to a reduction in chromosome number that is essential for sexual reproduction, and to an increase in genetic variation that is a driving force for evolution. Thus, the cell cycle plays a central role in the operation and development of all life, and in ensuring the continuity of life across generations. These discoveries were made over a period that extends into the previous century, and so the scope of this review will be similarly extended, hence “A Long Twentieth Century of the Cell Cycle.”