FEBS Letters Special Issue: Cell Cycle Control
Alexis R. Barr and Jörg Mansfeld
The cell cycle is the coordinated process of cell growth and division. Entry into and progression through the cell cycle must be tightly controlled to achieve normal development and tissue homeostasis. In mammalian cells, the cell cycle is divided into four stages: G1 (growth); S‐phase (DNA synthesis); G2 (growth); and mitosis (cell and nuclear division). A fifth stage resides outside the proliferative cycle and is known as quiescence (G0), where cells can reversibly exit the cell cycle. Transition through and between cell cycle stages is regulated by changes in cyclin‐dependent kinase (CDK) activity. Dysregulation of processes that impact CDK activity can lead to proliferative diseases, such as cancer or fibrosis, and, as such, research into the cell cycle has wide‐reaching implications for human health. In addition, as highlighted in this minireview series, the targeted manipulation of cell cycle progression may provide new avenues for regenerative therapies and induced pluripotency‐based approaches.
The last 50 years has seen fantastic achievements in the assembly of a parts list for cell cycle control. Beyond this, through elegant genetic studies in model organisms, molecular biology and imaging studies in cells and biochemical experiments in vitro and in cell extracts, we now have a grasp of how many of the components of this complex cell cycle machine interact with one another and where they localise in space and time. Most recently, new insights have been generated through the use of quantitative single‐cell approaches to tackle the problem of cell cycle heterogeneity, through genetic editing in mammalian systems to probe signalling pathways in exquisite detail, and by employing mathematical models to generate nonintuitive insights into the complex systems underpinning cell cycle control. Whilst it is difficult to accurately predict the future of a field, there is still much to be done in acquiring a truly quantitative view of protein–protein interactions in space and time that are a fundamental basis for cell cycle regulation, and in understanding the tissue specificity of control and the diverse mechanisms that achieve the same outcome. Work in this latter area should also help to design more specific therapies for cancer treatment and regenerative therapies dependent on the tissue or cell type of origin.
We have put together a collection of Review articles on cell cycle control. In this Special Issue, we present Part 1 of this collection, Part 2 will be published in early 2020. Part 1 starts with a review by Jeremy Purvis and colleagues  that provides an overview of how transitions between the cell cycle phases, whilst regulated by different CDK complexes, are governed by common principles, chiefly bistable switches. The second review, by Hilary Coller, tackles the often overlooked, but hugely important, role of metabolism in quiescence–proliferation transitions and covers how metabolic properties differ between multiple differentiated and stem cell states . This review is followed by that from Shanqgin Guo and colleagues  on the relationship between the speed of the cell cycle and cell fate commitment. The authors explore the intriguing observations that fast cycling cells are more permissive for reprogramming and discuss the molecular basis of this observation. Moving on, the next four reviews cover progress through the cell cycle and how cells transition into and through consecutive cell cycle phases. Jean Cook and Juanita Limas focus on how cells prepare for DNA replication during G1 and how the execution of these steps is essential for proper DNA replication in S‐phase . The next phase of the cell cycle is discussed in the review from Helfrid Hochegger's laboratory, who investigate the control of entry into mitosis . A number of overlapping pathways regulate the switch from G2 into M, and here, the authors discuss how these networks are coordinated to lead to robust mitotic entry. The review from Ulrike Gruneberg and colleagues  covers the mechanisms of how chromosome alignment and biorientation are achieved during mitosis, to ensure equal segregation of chromosomes into two new daughter cells. This process is monitored by the spindle assembly checkpoint, and here, the authors describe the intricate regulation of this final cell cycle checkpoint, necessary to avoid aneuploidy. Once chromosomes are aligned, anaphase can proceed and pathways controlling mitotic exit are activated. In a review from Francis Barr and colleagues , the roles of phosphatases in the controlled exit from mitosis are discussed. It is vital to achieve the correct temporal order of events such that, for example, chromosome segregation occurs before cytokinesis. The final review in this Special Issue moves us away from mitotic cell cycles and into meiosis. Having appreciated the roles of different cyclin/CDK complexes in mitotic cycles in the earlier reviews, in this review from Philipp Kaldis’ laboratory we now learn the roles for CDKs in gametogenesis. This review allows us to appreciate the complex and diverse roles of CDKs, beyond regulating cell cycle phase transitions, which are only just starting to be understood.
We hope you enjoy this Special Issue and look out for Part 2 in early 2020!
Alexis R. Barr is a Cancer Research UK Career Development Fellow and a team leader at the MRC‐LMS at Imperial College London. She started her research career in 2006 with Fanni Gergely at the CRUK Cambridge Institute, where she did her PhD research on mitotic spindle assembly and the role of centrosomes in this process. In 2010, Alexis moved to the Institute of Cancer Research in London to work with Chris Bakal. In Chris’ laboratory, Alexis started to use quantitative, high‐content, single‐cell imaging to address the question of how cell cycle entry is controlled, that is how do cells transition from G0 to G1 and from G1 to S. In 2018, Alexis moved to Imperial to start her own team to investigate proliferation–quiescence decisions in health and in cancer.
Jörg Mansfeld is a research group leader at the Biotechnology Centre of the TU Dresden in Germany. His fascination for cell cycle research began in 2004 during his PhD in Ulrike Kutay's laboratory at the ETH Zurich, where he investigated how nuclear pore complexes are assembled after mitosis into the reforming nuclear envelope. In 2008, Jörg joined Jonathon Pines’ group at the Wellcome Trust/Cancer Research UK Gurdon Institute in Cambridge to study the dynamic interplay between the spindle assembly checkpoint and its main target, the anaphase‐promoting complex/cyclosome (APC/C) ubiquitin E3 ligase. In 2013, Jörg moved back to Germany to start his own laboratory investigating how post‐translational modifications of cell cycle proteins by ubiquitin and reactive oxygen species in normal and stressed conditions govern the decision to divide or not to divide. (copyright belongs to Magdalena Gonciarz)
1. , , and (2019) Bistable switches as integrators and actuators during cell cycle progression. FEBS Lett. https://doi.org/10.1002/1873-3468.13628
2. (2019) .>span class="Apple-converted-space"> FEBS Lett. https://doi.org/10.1002/1873-3468.13608
3. and (2019) Cell cycle dynamics in the reprogramming of cellular identity. FEBS Lett. https://doi.org/10.1002/1873-3468.13625,
4. and (2019) Preparation for DNA replication: the key to a successful S phase. FEBS Lett. https://doi.org/10.1002/1873-3468.13619
5. and (2019) Triggering mitosis. FEBS Lett. https://doi.org/10.1002/1873-3468.13635
6. and (2019) Orchestration of the spindle assembly checkpoint by CDK1‐cyclin B1. FEBS Lett. https://doi.org/10.1002/1873-3468.13591,
7. and (2019) Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 AND PP2A. FEBS Lett. https://doi.org/10.1002/1873-3468.13595,
First published in FEBS Letters, Issue 593, 28 October 2019. doi:10.1002/1873-3468.13638
How to cite this Editorial: Barr, A.R. and Mansfeld, J. (2019), FEBS Letters Special Issue: Cell Cycle Control. FEBS Lett, 593: 2803-2804. doi:10.1002/1873-3468.13638