Cell Division

The cell cycle

The human cell cycle with Cdk1-Cyclin B control of the G2/M transition

Passage through the restriction point (RP) in G1 phase commits a cell to passage through the cell division cycle. DNA replication in S phase is separated from mitosis by a gap phase, G2. Transition through the major rate limiting commitment steps into the cycle, DNA replication (S) and genome segregation (M) is driven by CDK-Cyclin activities.

Defects in DNA integrity activate cell cycle checkpoints that block progression through key cell cycle transitions until the damage is restored. As the mutations that enable cancer cells to bypass normal growth controls lead to the accumulation of DNA damage and changes to the chromosome number, cancer cells become more reliant upon these checkpoints than their normal neighbours.

Consequently, agents that enhance DNA damage are widely used in the clinic as they increase the level of damage in the already stressed cancer cells to a point where checkpoint defenses are unable to prevent catastrophic division. By contrast, their normal neighbours simply extend their cell cycle times to accommodate the elevated level of damage. We are therefore asking how these checkpoints operate to find ways to manipulate checkpoint controls in a manner that will selectively eliminate cancer cells.

A diagram of the cell cycle showing some of the key steps in the cycle

Research areas

Mitotic commitment control

The observation that active CDK1-Cyclin B appears on human centrosomes before propagating throughout the cell has been consolidated by other data to suggest that the centrosome provides a specific microenvironment for the activation of CDK1-Cyclin B to trigger the G2/M transition.
Our studies of the fission yeast centrosome equivalent, the spindle pole body (SPB), provide molecular insight into how this switch may operate.

Regulation in checkpoint control

The transition from G2 phase into mitosis is driven by activation of the CDK1-Cyclin B protein kinase. CDK1-Cyclin B activity is restrained through inhibitory phosphorylation by the WEE1 family kinases WEE1 and PKMYT1. When the time is right, the inhibitory phosphate is removed by CDC25 phosphatases and cells enter mitosis.

Mitotic commitment control
Regulation in checkpoint control

A note from the Group Leader – Iain Hagan

We exploit genetic malleability of fission yeast as a model organism to study three aspects of the control and execution of cell division: mitotic commitment, mitotic exit and mitotic kinase function. We then apply the lessons learned from yeast to the interrogation of the same processes in the complex human cell divisions. 

Meet the group

It’s a great pleasure to introduce the Cell Division group, who are a joy to work with as they are always eager to support each other and welcome new members to the teamThey are dedicated to their research and the work we do in our lab. And I am delighted to say that they also find time to have fun as well!

Iain Hagan

Senior Group Leader

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Asma Belbelazi

Postdoctoral Fellow

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Keren Dawson

Senior Scientific Officer

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Zoe Edwards

Senior Scientific Officer

Charlie Greenaway-Wells PhD Student
Charlie Greenaway-Wells

PhD Student

Lenka Halova Senior Scientific Officer
Lenka Halova

Senior Scientific Officer

Portrait image of Scientist Daniela Mclaverty
Daniela McLaverty

Senior Scientific Officer

Pawan Singh Senior Scientific Officer
Pawan Singh

Senior Scientific Officer

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Wendy Trotter

Senior Scientific Officer

Pawan Singh winning the best poster prize

Sharing successes

Colloquium 2024 Best Poster Prize winner

At the Institute’s annual Colloquium, the 2024 Best Poster Prize for a scientific officer went to Pawan Singh of the Cell Division group for his outstanding work on converting rising cdk1-cyclin b levels into a switch for mitotic commitment via feedback control from the fission yeast spindle pole body.

All Institute Publications

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https://doi.org/10.1186/s12943-024-02157-x

The PI3K-AKT-mTOR axis persists as a therapeutic dependency in KRASG12D-driven non-small cell lung cancer

12 November 2024

Institute Authors (1)

Amaya Viros

Labs & Facilities

Genome Editing and Mouse Models

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Research Group

Skin Cancer & Ageing

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https://doi.org/10.1186/s13045-024-01610-0

The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency

8 October 2024

Institute Authors (6)

Georges Lacaud, Mathew Sheridan, Michael Lie-a-ling, Liam Clayfield, Jessica Whittle, Jingru Xu

Research Group

Stem Cell Biology

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/wp-content/uploads/2024/11/Annual-Report-2023.pdf

2023 Annual Report

13 September 2024

https://doi.org/10.1126/science.adh7954

Vitamin D regulates microbiome-dependent cancer immunity

25 April 2024

Institute Authors (1)

Evangelos Giampazolias

Research Group

Cancer Immunosurveillance

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https://doi.org/10.1038/s41684-024-01363-w

Streamlining mouse genome editing by integrating AAV repair template delivery and CRISPR-Cas electroporation

10 April 2024

Institute Authors (1)

Natalia Moncaut

Labs & Facilities

Genome Editing and Mouse Models

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https://www.biorxiv.org/content/10.1101/2023.12.13.568969v1

A novel human model to deconvolve cell-intrinsic phenotypes of genetically dysregulated pathways in lung squamous cell carcinoma

14 December 2023

Institute Authors (3)

Carlos Lopez-Garcia, Caroline Dive, Anthony Oojageer

Research Group

Translational Lung Cancer Biology

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