Figure S4 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors
<p>Supplementary Figure S4. Impact on DNA replication, cell cycle, and apoptosis with PARP inhibitor treatment in BRCA2 wildtype and mutant cells – related to Figure 5. A) Graph showing quantification of % EdU-positive ‘S’ phase cells. DLD-1 BRCA2 mutant control or POLB knockout cells treated with 500 nM niraparib for 5 days followed by staining with Click-iT EdU flow cytometric assay. FACS data was analyzed by FloJo software. B) Histogram plots of cell cycle analysis using a propidium iodide assay in DLD-1 BRCA2 WT control or POLB knockout cells treated with 500 nM niraparib for 5 days (left). Quantification of each cell cycle phase (% cells) across all treatment conditions is shown in the graph (right). C) FACS plots showing apoptosis analysis with Annexin-V/PI staining in DLD-1 BRCA2 WT control or POLB knockout cells treated with 500 nM niraparib for 7 days (left). Quantification of % apoptotic cells (annexin V positive + annexin-V/PI positive) is shown for all the conditions tested (right).</p>
Authors
- Brian Doyon
- Madhavi Bandi (ORCID: https://orcid.org/0000-0002-7562-0170)
- Tianshu Feng (ORCID: https://orcid.org/0000-0002-9445-4876)
- William D. Mallender
- Robert Tjin Tham Sjin (ORCID: https://orcid.org/0000-0002-3809-8424)
- Jannik N. Andersen (ORCID: https://orcid.org/0000-0003-4528-2120)
- Erik Wilker (ORCID: https://orcid.org/0000-0003-4535-178X)
- Douglas A. Whittington (ORCID: https://orcid.org/0000-0002-5946-8543)
- Alan Huang (ORCID: https://orcid.org/0000-0001-5501-0212)
- Yi Yu (ORCID: https://orcid.org/0000-0002-2223-337X)
- Xuewen Pan (ORCID: https://orcid.org/0000-0002-0148-5631)
- Katherine Lazarides (ORCID: https://orcid.org/0000-0002-0878-0465)
- Shangtao Liu (ORCID: https://orcid.org/0000-0002-2724-9178)
- Hongxiang Zhang (ORCID: https://orcid.org/0000-0001-6794-0038)
- Ashley H. Choi (ORCID: https://orcid.org/0000-0002-2802-7163)
- Justin L. Engel (ORCID: https://orcid.org/0000-0002-2016-3494)
- Binzhang Shen (ORCID: https://orcid.org/0000-0002-6556-7791)
- Samuel R. Meier (ORCID: https://orcid.org/0000-0002-7026-2722)
- Brian J. McMillan (ORCID: https://orcid.org/0000-0002-3134-7774)
- Michele Meseonznik
Publication Details
- Published
- 2025-09-02
- DOI
- https://doi.org/10.1158/1535-7163.30028931
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00