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  1. Article ; Online: Sirtuin inhibition is synthetic lethal with BRCA1 or BRCA2 deficiency

    Ilirjana Bajrami / Callum Walker / Dragomir B. Krastev / Daniel Weekes / Feifei Song / Andrew J. Wicks / John Alexander / Syed Haider / Rachel Brough / Stephen J. Pettitt / Andrew N. J. Tutt / Christopher J. Lord

    Communications Biology, Vol 4, Iss 1, Pp 1-

    2021  Volume 16

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets

    Dragomir B. Krastev / Stephen J. Pettitt / James Campbell / Feifei Song / Barbara E. Tanos / Stoyno S. Stoynov / Alan Ashworth / Christopher J. Lord

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: Poly ADP-ribosylation (PARylation) is a highly dynamic post-translation protein modification, but most methods only detect stable PARylation events. Here the authors develop a split-GFP-based sensor for PARylation detection in live cells and use it to ... ...

    Abstract Poly ADP-ribosylation (PARylation) is a highly dynamic post-translation protein modification, but most methods only detect stable PARylation events. Here the authors develop a split-GFP-based sensor for PARylation detection in live cells and use it to identify a new centrosomal PARylation target.
    Keywords Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  3. Article ; Online: Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets

    Dragomir B. Krastev / Stephen J. Pettitt / James Campbell / Feifei Song / Barbara E. Tanos / Stoyno S. Stoynov / Alan Ashworth / Christopher J. Lord

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: Poly ADP-ribosylation (PARylation) is a highly dynamic post-translation protein modification, but most methods only detect stable PARylation events. Here the authors develop a split-GFP-based sensor for PARylation detection in live cells and use it to ... ...

    Abstract Poly ADP-ribosylation (PARylation) is a highly dynamic post-translation protein modification, but most methods only detect stable PARylation events. Here the authors develop a split-GFP-based sensor for PARylation detection in live cells and use it to identify a new centrosomal PARylation target.
    Keywords Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance

    Stephen J. Pettitt / Dragomir B. Krastev / Inger Brandsma / Amy Dréan / Feifei Song / Radoslav Aleksandrov / Maria I. Harrell / Malini Menon / Rachel Brough / James Campbell / Jessica Frankum / Michael Ranes / Helen N. Pemberton / Rumana Rafiq / Kerry Fenwick / Amanda Swain / Sebastian Guettler / Jung-Min Lee / Elizabeth M. Swisher /
    Stoyno Stoynov / Kosuke Yusa / Alan Ashworth / Christopher J. Lord

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, ... ...

    Abstract The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, suggesting alternative resistance mechanisms.
    Keywords Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance

    Stephen J. Pettitt / Dragomir B. Krastev / Inger Brandsma / Amy Dréan / Feifei Song / Radoslav Aleksandrov / Maria I. Harrell / Malini Menon / Rachel Brough / James Campbell / Jessica Frankum / Michael Ranes / Helen N. Pemberton / Rumana Rafiq / Kerry Fenwick / Amanda Swain / Sebastian Guettler / Jung-Min Lee / Elizabeth M. Swisher /
    Stoyno Stoynov / Kosuke Yusa / Alan Ashworth / Christopher J. Lord

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 14

    Abstract: The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, ... ...

    Abstract The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, suggesting alternative resistance mechanisms.
    Keywords Science ; Q
    Language English
    Publishing date 2018-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  6. Article ; Online: A genetic screen using the PiggyBac transposon in haploid cells identifies Parp1 as a mediator of olaparib toxicity.

    Stephen J Pettitt / Farah L Rehman / Ilirjana Bajrami / Rachel Brough / Fredrik Wallberg / Iwanka Kozarewa / Kerry Fenwick / Ioannis Assiotis / Lina Chen / James Campbell / Christopher J Lord / Alan Ashworth

    PLoS ONE, Vol 8, Iss 4, p e

    2013  Volume 61520

    Abstract: Genetic perturbation screens have the potential to dissect a wide range of cellular phenotypes. Such screens have historically been difficult in diploid mammalian cells. The recent derivation of haploid embryonic stem cells provides an opportunity to ... ...

    Abstract Genetic perturbation screens have the potential to dissect a wide range of cellular phenotypes. Such screens have historically been difficult in diploid mammalian cells. The recent derivation of haploid embryonic stem cells provides an opportunity to cause loss of function mutants with a random mutagen in a mammalian cell with a normal genetic background. We describe an approach to genetic screens that exploits the highly active piggyBac transposon in haploid mammalian cells. As an example of haploid transposon (HTP) screening, we apply this approach to identifying determinants of cancer drug toxicity and resistance. In a screen for 6-thioguanine resistance we recovered components of the DNA mismatch repair pathway, a known requirement for toxicity. In a further screen for resistance to the clinical poly(ADP-ribose) polymerase (PARP) inhibitor olaparib we recovered multiple Parp1 mutants. Our results show that olaparib toxicity to normal cells is mediated predominantly via Parp1, and suggest that the clinical side effects of olaparib may be on target. The transposon mutant libraries are stable and can be readily reused to screen other drugs. The screening protocol described has several advantages over other methods such as RNA interference: it is rapid and low cost, and mutations can be easily reverted to establish causality.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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