Out-licensing

Novel Tumour Suppressors: The Human G2 Checkpoint Genes

Introduction/Background

Normal eukaryotic cells cease to divide when they experience damage to the DNA caused by chemotherapy or radiation. This phenomenon is termed the "DNA damage-induced checkpoint response". These checkpoints in the cell division cycle play a critical role in the maintenance of genomic integrity. Cells that are mutated in one of the cell cycle checkpoint genes are unable to stop cell cycle progression even in the presence of DNA damage. This can lead to increased rates of tumour formation and therefore checkpoint genes are termed tumour
suppressors.

Aims/Hypothesis

We are investigating human G2 checkpoint genes.

Research

Many of the checkpoint genes and their signalling pathways have been characterized using yeast cells. Our scientists have identified, sequenced and expressed the human RAD17, RAD1, and HUS1, which are critical for ensuring that the cell does not progress through the G2 checkpoint until DNA replication, DNA repair, and chromosome duplication are complete. In yeast systems, these proteins have protein kinase activity and are involved in generating a signal to block the cell cycle in response to DNA damage. Since signalling systems controlling the cell cycle are conserved from yeast cells to human cells, it is very likely that the human G2 checkpoint genes will also play a role in cell cycle regulation in human cells as tumour suppressors.

Conclusion

RAD17, RAD1, and HUS1 are critical G2 checkpoint proteins that are likely to function as tumour suppressors, making them very attractive candidates for gene therapy development. Since these genes are newly identified, they are valuable targets for generating reagents, such as protein expression systems, antibodies, diagnostic tools, transgenic mice.

Relevance/Opportunity

Please enquire quoting reference no. RU 383 regarding licensing or codevelopment partnerships.

Preclinical

U.S. Patent Issued Sept. 24, 2002: #6,455,681 B1