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Steve Jackson

2017 Jackson

Steve Jackson PhD FRS FMedSci, Frederick James Quick Professor of Biology, Member of the Biochemistry Department. 

Jackson Group website | Europe PMC | Pubmed

 

 


Maintenance of genome stability

DNA is constantly damaged by environmental and endogenously arising agents. Cell survival and genome integrity are promoted by the DNA damage response (DDR), which detects, signals the presence of and repairs DNA damage. 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 DDR pathways, and to apply this knowledge to better understand and treat human diseases. We are also developing approaches to identify new DDR components and their functions.

For example, through synthetic viability screening, we recently identified a chromatin post-translational modification that drives sensitivity of cells to the anticancer drug camptothecin, and have shown how similar screens in yeast and mammalian cells can identify functional protein domains that impart drug sensitivity/resistance.

With colleagues at the MRC Epidemiology Unit, Cambridge, we identified genetic variants associated with Y chromosome loss, with implications for genome instability and cancer susceptibility.

Finally, we are using CRISPR-Cas9 synthetic viability screens to identify novel DDR proteins and define drug-resistance mechanisms.

Selected publications:

• Dev H et al. (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 et al. (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.

• Herzog M et al. (2018) Detection of functional protein domains by unbiased genome-wide forward genetic screening. Sci Rep. 8(1):6161. doi: 10.1038/s41598-018-24400-4.

• Blackford AN & Jackson SP. (2017) ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response. Mol Cell. 66(6):801-817. doi:10.1016/j.molcel.2017.05.015.

• Forment JV et al. (2017) Genome-wide genetic screening with chemically mutagenised haploid embryonic stem cells. Nat Chem Biol. 13(1):12-14. doi:10.1038/nchembio.2226.

• Balmus G et al. (2016) Synthetic lethality between PAXX and XLF in mammalian development. Genes Dev. 30(19):2152-2157. doi:10.1101/gad.290510.116

Jackson Group 2017

Video: Meet Steve Jackson

Co-workers

Inigo Ayestaran • Linda Baskcomb • Rimma Belotserkovskaya • Ramsay Bowden • Julia Coates • Muku Demir • Harveer Dev • Kate Dry • Yaron Galanty • Maryam Ghaderi Najafabadi • Soren Hough • Rebecca Lloyd • Donna Lowe • Maria Martin Agudo • David Morales • Francisco Muñoz Martinez • Dominic Pilger • Fabio Puddu • Elisenda Raga Gil • Helen Reed • Israel Salguero Corbacho • Matylda Sczaniecka-Clift • John Thomas