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Department of Biochemistry

 
Steve Jackson

Maintenance of genome stability.

 

The cells in our bodies are constantly being exposed to agents that damage our DNA, such as sunlight, or chemicals, in for example cigarette smoke, and also agents that occur naturally as part of normal cell metabolism. Cells have evolved a complex system, termed the DNA damage response (DDR) that detects DNA damage, signals its presence to the cell and sets about repairing this damage. The DDR is crucial for cell survival and to guard against cancer.

In the Jackson Group we are trying to understand how cells respond when their DNA is damaged, in particular how proteins signal and repair DNA double strand breaks. It is hoped that, together with the work of others, such research will indicate how defects in the DNA damage response can lead to diseases such as cancer, neurodegenerative diseases and premature ageing, and how such diseases might be better diagnosed and treated.

 

Research objectives

  • Study the structure and function of known DDR proteins, and identify important new DDR proteins and determine how these function in mammalian cells.

  • Explore how DDR events are affected by chromatin structure, cell cycle status and other parameters such as post-translational modifications.

  • Use new technologies such as gene editing and whole genome sequencing to explore the sensitivities/resistance mechanisms of DDR proteins in response to DNA-damaging agents and DDR inhibitors. This may identify potential therapeutic targets for generating new anti-cancer agents.

 

Key publications

Salguero I, Belotserkovskaya R, Coates J, Sczaniecka-Clift M, Demir M, Jhujh S, Wilson MD, Jackson SP (2019). MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance. Nat. Commun., 10(1):5191. doi: 10.1038/s41467-019-12929-5

Puddu F, Herzog M, Selivanova A, Wang S, Zhu J, Klein-Lavi S, Gordon M, Meirman R, Millan-Zambrano G, Ayestaran I, Salguero I, Sharan R, Li R, Kupiec M, Jackson SP (2019). Genome architecture and stability in the Saccharomyces cerevisiae knockout collection. Nature, 573(7774):416-420. doi: 10.1038/s41586-019-1549-9

Dev H, Chiang TW, Lescale C, de Krijger I, Martin AG, Pilger D, Coates J, Sczaniecka-Clift M, Wei W, Ostermaier M, Herzog M, Lam J, Shea A, Demir M, Wu Q, Yang F, Fu B, Lai Z, Balmus G, Belotserkovskaya R, Serra V, O'Connor MJ, Bruna A, Beli P, Pellegrini L, Caldas C, Deriano L, Jacobs JJL, Galanty Y, Jackson SP (2018). Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells. Nat. Cell Biol., 20(8):954-965. doi: 10.1038/s41556-018-0140-1

Balmus G, Larrieu D, Barros AC, Collins C, Abrudan M, Demir M, Geisler NJ, Lelliott CJ, White JK, Karp NA, Atkinson J, Kirton A, Jacobsen M, Clift D, Rodriguez R, Sanger Mouse Genetics Project, Adams DJ, Jackson SP (2018). Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome. Nat. Commun., 9(1):1700. doi: 10.1038/s41467-018-03770-3

Jackson SP, Bartek J (2009). The DNA-damage response in human biology and disease. Nature, 461(7267):1071-1078. doi: 10.1038/nature08467

Contact details

Opportunities

The Jackson Group is accepting enquiries from prospective interns, undergraduate students, postgraduate students and postdoctoral researchers.