skip to primary navigationskip to content
 

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 lab we are trying to understand how cells respond when their DNA is damaged, in particular how proteins signal and repair DNA double strand breaks.

Our aims are to: identify important DDR-proteins; determine how these proteins function; see how DDR events are affected by chromatin structure; and understand how the DDR impinges on diverse cellular events. 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 aging, and how such diseases might be better diagnosed and treated.

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

Visit group website at the Gurdon Institute

Key publications:

1. Dev H, et al. (2018) Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells. Nature Cell Biology 20, 954-965.

2. Balmus G, et al. (2018) Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome. Nature Communications 9, 1700.

3. Herzog M, et al.(2018) Detection of functional protein domains by unbiased genome-wide forward genetic screening. Scientific Reports 8, 6161.

4. Blackford AN and Jackson SP. (2017) ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response. Molecular Cell 66, 801-817.

5. Forment JV, et al. (2017) Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells. Nature Chemical Biology 13, 12-14.

6. Balmus G, et al. (2016) Synthetic lethality between PAXX and XLF in mammalian development. Genes and Development 30, 2152-2157.

7. Schmidt CK, et al. (2015) Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair. Nature Cell Biology 17, 1458-1470. ^Co-corresponding authors

8. Wijnhoven P, Konietzny R, Blackford AN, Travers J, Kessler BM, Nishi R, Jackson SP. (2015) USP4 auto-deubiquitylation promotes homologous recombination. Molecular Cell 60, 362-373.

9. Puddu F, et al. (2015) Synthetic viability genomic screening defines Sae2 function in DNA repair. EMBO Journal 34, 1509-22. *These authors contributed equally to this work.

10. Ochi T, et al. (2015) PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science 347, 185-188.

11. Davies OR, et al. (2015) CtIP tetramer assembly is required for DNA-end resection and repair. Nature Structural and Molecular Biology 22, 150-157.

12. Nishi R, et al. (2014) Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity. Nature Cell Biology 16, 1016-1026.

13. Larrieu D, Britton S, Demir M, Rodriguez R, Jackson SP. (2014) Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science 344, 527-532.

14. Galanty Y, Belotserkovskaya R, Coates J, Jackson SP. (2012) RNF4, a SUMO-targeted ubiquitin E3 ligase, promotes DNA double-strand break repair. Genes Dev. 26, 1179-95.

15. Jackson SP and Bartek J. (2009) The DNA damage response in human biology and disease. Nature 461, 1071-1078.