Northern Institute for Cancer Research

Cell Cycle Structural Biology

Cell Cycle Structural Biology

About

We adopt a structure-based approach to understand how CDK-cyclins work. We look at how they are regulated, and how their inappropriate activity can contribute to the development of disease.

Research Leaders

Jane Endicott
Martin Noble

Our research

The behaviour of a cell is defined by the set of genes it expresses and by its commitment to either a quiescent or proliferating state. The cyclin-dependent kinases (CDKs) bind to non-catalytic cyclin subunits to form CDK-cyclin complexes. 

These play central roles in regulating both gene-expression and cell-proliferation.  CDK-cyclins are important in normal cells and in a variety of disease conditions.

Characterising the CDK family

Our group studies CDK family members involved in both cell cycle (CDK1, 2, 4 and 6) and transcriptional (CDK7 and CDK9) processes. 

In the mitotic cell cycle, sequential waves of CDK-cyclin activity promote and co-ordinate alternating rounds of DNA replication and chromosome segregation. They respond to checkpoint pathways to ensure the genomic integrity of each daughter cell. 

Coordinated phosphorylation of the RNA polymerase II (Pol II) C-terminal domain by CDK7, CDK8 and CDK9 acting within large macromolecular complexes regulates Pol II activity and its assembly. It does this through transcription factors and regulators to control transcription initiation and elongation. 

CDK regulation

The expansion of the CDK family in higher eukaryotes reflects a requirement to integrate and finely tune the response to signals generated by a multicellular environment. This allows tissue-specific functions to evolve.

Development of CDK inhibitors

We collaborate with colleagues in the Drug Discovery Group and elsewhere to develop potent and selective CDK inhibitors as probes. These help understand CDK activity and can become leads for drug design.

Staff

Staff

Richard Heath
Svitlana Korolchuk
Martyna Pastok
Marco Salamina


Postgraduate students

Stephen Hallett
Daniel Wood