Research Interests

DNA damage responses and their integration with DNA replication and the cell cycle

Research Area

My Laboratory is interested in the mechanisms that maintain genome integrity and cell cycle control. DNA is constantly subjected to damage by endogenous and exogenous factors. If the DNA is not repaired then mutations can be generated which if allowed to persist, can lead to the development of diseases such as cancer. In order to ensure genome integrity, cells have evolved complex surveillance mechanisms to protect the integrity of the genome. DNA damage responses, detect damaged DNA or stalled DNA replication and can initiate a range of cellular responses such as cell cycle arrest, DNA repair, or if damage is too extensive, to destroy the cell through apoptosis. Mutations in several components in these pathways lead to human diseases that are characterised by a predisposition to certain cancers as well as developmental and neurological abnormalities. Therefore, an understanding of how these pathways operate and impinge on other cellular processes is vital if human diseases such as cancer and developmental abnormalities are to be understood and treated successfully. The importance of these pathways is illustrated by the fact that the components have been highly conserved through evolution between yeast and humans.

Current Members

Lindsay, Howard D (Principal Investigator/Director)
Ford, Christopher C (Other)

Additional Information

In our work we use cell-free extracts made from the eggs of Xenopus laevis as a simple model system. These extracts recapitulate cell cycle events such as DNA replication and mitosis in vitro and are a versatile and powerful tool with which to dissect these complex signaling pathways. Xenopus also provides the opportunity to analyse the regulation of these pathways during development.Our main focus has been concerned with the DNA checkpoint proteins, in particular the role of the XRad17/RFC, XRad9/Rad1/Hus1 and Atr/Atrip complexes in the DNA replication checkpoint. This work is continuing along with projects concerning the repair of double strand DNA breaks by non-homologous endjoining (NHEJ) and the involvement of chromatin modifying factors reqyured for the initiation of DNA replication and the checkpoint response.

Contact

Institution: Lancaster University

Address:
Biomedical and Life Sciences
School of Health and Medicine
Lancaster University
Bailrigg
Lancaster, Lancashire
LA1 4YQ, United Kingdom

Web Page: https://www.lancaster.ac.uk/health-and-medicine/about-us/people/howard-lindsay