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Showing 1–5 of 5 results
Advanced filters: Author: "Stephen Pettitt" Clear advanced filters

  • Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP inhibitor resistance caused by 53BP1/Shieldin pathway defects.

    • Diana Zatreanu
    • Helen M. R. Robinson
    • Christopher J. Lord
    ResearchOpen Access
    Nature Communications
    Volume: 12, P: 1-15

  • Krastev et al. report that trapped PARP1 undergoes SUMOylation, followed by ubiquitylation, resulting in the recruitment of the p97 ATPase to remove trapped PARP1 from chromatin and prevent PARP inhibitor-induced cytotoxicity.

    • Dragomir B. Krastev
    • Shudong Li
    • Christopher J. Lord
    ResearchOpen Access
    Nature Cell Biology
    Volume: 24, P: 62-73

  • This Perspective article explores complex synthetic lethal relationships in cancer, which can involve several partners. Understanding this complexity presents challenges and opportunities for the development of therapeutics that target these interactions.

    • Colm J. Ryan
    • Lovely Paul Solomon Devakumar
    • Christopher J. Lord
    Reviews
    Nature Genetics
    Volume: 55, P: 2039-2048

  • Bajrami, Walker et al. investigated the synthetic lethality between BRCA gene defects and inhibition of two sirtuin genes, SIRT1 or SIRT6, which was found to be associated with replication stress and increased PARylation. The authors demonstrated that the SIRT/BRCA1 synthetic lethality was reversed by genetic ablation of PARP1 or HPF1.

    • Ilirjana Bajrami
    • Callum Walker
    • Christopher J. Lord
    ResearchOpen Access
    Communications Biology
    Volume: 4, P: 1-16