Editorial

Abstract

We are delighted to publish Part 2 of our Special Issue on cell cycle control. Here, we present four reviews that, together with Part 1, give a comprehensive overview of our current understanding of the cell cycle, as well as the methods employed to study it, the roles of cell cycle proteins beyond orchestrating cell division, and some of the key outstanding questions. Part 1 provided an overview of the common principles governing the transitions between the cell cycle phases [1], the role of metabolism in quiescence–proliferation transitions [2] and the relationship between the speed of the cell cycle and cell fate [3]. In addition, Part 1 covered how cells prepare for DNA replication during G1 and how this impacts proper DNA replication in S-phase [4], how cells control entry into mitosis [5] and, once in mitosis, how they achieve proper chromosome alignment and equal segregation of chromosomes into two daughter cells [6], and how mitotic exit is controlled to ensure appropriate temporal and spatial organisation [7]. A comparison between the function of CDKs in mitosis and meiosis concluded Part 1 [8]. Part 2 begins with a review from Silvia Santos’ Lab that covers how embryonic cell cycles remodel in order to give rise to somatic cell cycles, including the, often forgotten, differences between human and mouse embryonic stem cells [9]. Adaptation of embryonic cell cycles to somatic cell cycles requires extensive changes in the regulation of cyclins, CDKs and the anaphasepromoting complex/cyclosome, as well as the introduction of cell cycle checkpoints. A notable example of the checkpoints that are introduced en route to somatic cell cycles is the restriction point. The restriction point is defined as the point in the cell cycle beyond which cells no longer require input from mitogens to complete cell division. In a review from our laboratory, we discuss and analyse recent data to understand the control of the restriction point in determining proliferation–quiescence decisions in cells [10]. The restriction point was originally defined over 40 years ago, yet its position within the cell cycle and the molecular basis for this decision are still active topics of investigation. From proliferation–quiescence decisions, we then move onto proliferation–differentiation decisions, in a review from the Kimata and Aradhya laboratories [11]. Much has been written in this review series about the roles of cyclin:CDK complexes in driving the cell cycle. However, here the focus is on the cell cycle-independent roles of cyclins, CDKs and their inhibitors, in particular in their contributions to cell differentiation. It is critical to remember these non-cell cycle functions, particularly when analysing the phenotypes of mice where the function of these proteins has been disrupted. Finally, Anna Eastman and Shangqin Guo have provided a second review for this series, and this one focussed on the methods available to study and probe the cell cycle [12]. We imagine that this will be of particular interest to researchers new to the field but also serves as a very useful reminder to experts as to the strengths and weaknesses of our assays. We anticipate that readers new to the cell cycle field and also aficionados of cell cycle control will enjoy this special issue. Hopefully, these reviews, written by leaders in cell cycle research, will spark new questions and ideas to keep expanding our understanding of the phenomenal and beautiful process that is cell division.