The Jackson Group

Maintenance of genome stability

DNA is constantly damaged by environmental and endogenously arising agents. Cell survival and genome integrity are promoted by DNA repair and associated processes, collectively known as the DNA-damage response (DDR). DDR defects are associated with developmental disorders, immunodeficiencies, infertility, premature ageing and cancer.

Our research aims to characterise the cell biology and mechanisms of established and new DDR components and pathways, and to identify ways to translate this knowledge to better understand and treat human diseases.

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We have developed strong expertise in CRISPR-based gene-editing and screening technologies (top panel), which together with focused mechanistic studies, have allowed us to successfully interrogate and identify new players in DNA damage responses, including in clinically relevant settings.

In our latest review article, we discuss the mechanistic basis of CRISPR-Cas genetic screening approaches and describe how they have contributed to our understanding of DNA repair and DDR pathways. Furthermore, we have created the DDR CRISPR screen (DDRcs) portal, in which we have collected and reanalysed data from CRISPR screen studies and provide a tool for systematically exploring them (bottom panel).

Schematic showing a general CRISPR-screening strategy to identify genes that confer sensitivity or resistance to a particular drug. MOI: multiplicity of infection. This ensures that only one gene per cell is knocked out.
Example output from the DDRcs Portal showing CRISPR screen results for three selected genes, ATM, ATR and PRKDC (DNAPKcs), reported in the published literature.