Steve Jackson

Head of Cancer Research UK laboratories

Research summary

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.

Expand summary

We have developed strong expertise in CRISPR-based gene-editing and screening technologies, 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.

For example, we assessed the impact of cellular p53 status on CRISPR-Cas9 screen performance; findings that highlight key factors for performing successful, robust screens in the future. Furthermore, we used CRISPR screens to explore mechanisms of anti-cancer drug resistance in cells proficient or deficient for the key DDR protein kinase ATM (A). We identified novel biomarkers that might be used to identify which cancers will respond to treatment with drugs that are currently in clinical development, thus helping in patient stratification and pre-empting drug resistance (B).

We have also recapitulated human cancer-causing DNA polymerase mutations in yeast, giving insights into how certain mutations can lead to high levels of mutagenesis and tumourigenesis.

Lloyd et al Fig 3A+B NAR Aug 2021

Steve Jackson colour portrait

Selected publications

  • Herzog M et al. (2021) Mutagenic mechanisms of cancer-associated DNA polymerase ϵ alleles. Nucleic Acids Research 49(7): 3919-3931. DOI: 10.1093/nar/gkab160.

    March 25, 2021

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  • Lloyd RL et al. (2021) Loss of Cyclin C or CDK8 provides ATR inhibitor resistance by suppressing transcription-associated replication stress. Nucleic Acids Res 49(15):8665-8683. DOI 10.1093/nar/gkab628.

    July 30, 2021

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  • Bowden AR et al. (2020) Parallel CRISPR-Cas9 screens clarify impacts of p53 on screen performance. eLife 9:e55325. DOI: 10.7554/eLife.55325.

    May 22, 2020

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  • Belotserkovskaya R et al. (2020) PALB2 chromatin recruitment restores homologous recombination in BRCA1-deficient cells depleted of 53BP1. Nature Communications 11: 819. DOI: 10.1038/s41467-020-14563-y.

    February 10, 2020

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  • Salguero I et al. (2019) MDC1 PST-repeat region promotes histone H2AX- independent chromatin association and DNA damage tolerance. Nature Communications 10: 5191. DOI: 10.1038/s41467-019-12929-5.

    November 15, 2019

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  • Puddu F et al. (2019) Genome architecture and stability in the Saccharomyces cerevisiae knockout collection. Nature 537:416-420. DOI: 10.1038/s41586-019-1549-9.

    September 11, 2019

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  • Balmus G et al. (2019) ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks. Nat Commun 10(1):87. DOI: 10.1038/s41467-018-07729-2.

    January 8, 2019

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  • 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.

    July 18, 2018

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  • 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.

    April 27, 2018

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Biography

Prof Steve Jackson PhD FRS FMedSci
Head of Institute’s Cancer Research UK laboratories, Frederick James Quick Professor of Biology, Member of the University Department of Biochemistry

My academic research aims to better understand how cells detect and repair DNA damage and signal its presence to affect myriad aspects of cell biology. My laboratory has a strong track record of using a broad range of cell and molecular biological techniques and approaches, in both mammalian and yeast cells.

My discovery that DNA breaks trigger DNA-PK kinase activity established a paradigm for DNA damage detection and signalling, leading us to identify the first non-homologous end-joining (NHEJ) DNA-repair proteins. Subsequently, we identified and/or determined functions for these and other core NHEJ proteins, showing how they and additional DDR factors interact in regulated ways.

We have defined many aspects of the DDR, particularly those controlling and/or mediated by phosphorylation, ubiquitylation, sumoylation and/or chromatin modifications. In 1995, we found that DDR-enzyme-targeting compounds could selectively kill cancer cells, and that defects in some cause DNA-damage hypersensitivity in the absence of others.

Knowing that DDR defects occur in cancer, I founded KuDOS Pharmaceuticals: the world’s first DNA-repair company. KuDOS developed the innovative precision anti-cancer medicine olaparib/LynparzaTM that is enhancing and extending the lives of thousands of patients worldwide. My academic laboratory is currently further defining mechanisms of DNA repair and associated processes, with a view to delivering new biological insights and identifying new therapeutic opportunities for cancer and other diseases.

It is my belief that a deeper knowledge of DNA repair and DDR pathways will yield better understandings of diseases that arise when such pathways are impaired or deregulated.

Notable achievements and honours

  • 2020
    Royal Society Mullard Award
  • 2019
    Fondation ARC Léopold Griffuel Award for Translational and Clinical Research
  • 2016
    Royal Netherlands Academy of Arts and Sciences Dr. A.H. Heineken Prize for Medicine
  • 2016
    King Faisal International Prize for Science
  • 2015
    Gagna A. & Ch. Van Heck Prize
  • 2011
    Royal Society Buchanan Medal
  • 2008
    Fellow of the Royal Society
  • 2001
    Academy of Medical Sciences, UK

Research group

  • Dr Samah Awad Diab

    Research Associate

  • Dr Aldo Bader

    Research Associate

  • Dr Rimma Belotserkovskaya

    Senior Research Associate

  • Dr Chris Carnie

    Research Associate

  • Julia Coates

    Research Assistant

  • Dr Giuseppina D'Alessandro

    AIRC iCARE-2 Fellow

  • Muku Demir

    Research Assistant

  • Dr Kate Dry

    Information Specialist

  • Dr Yaron Galanty

    Senior Research Associate

  • Chen Gang Goh

    PhD Student

  • Nadia Gueorguieva

    Research Assistant

  • Soren Hough

    PhD Student/ Research Assistant

  • Donna Lowe

    PhD Student

  • David Morales

    PhD Student

  • Dr Fabio Puddu

    PhD Student

  • Dr Matylda Sczaniecka-Clift

    Research Associate

  • Dr Almudena Serrano Benitez

    Research Associate

  • Dr John Thomas

    Research Associate

  • Andrea Voigt

    Research Assistant

  • Mike Woods

    Bioresearch Manager