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September 5, 2025Open Access

Figure S3 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors

Key Points

POLB knockout significantly enhances the effectiveness of PARP inhibition in BRCA1-mutant tumor cells.
Control and POLB knockout cell lines showed marked differences in response to niraparib and olaparib treatments.
Dose response curves demonstrated that POLB loss dramatically reduces cell viability when combined with PARP inhibitors.
Statistical analysis confirmed a strong correlation between POLB knockout and increased sensitivity to PARP inhibitors.

Abstract

Supplementary Figure S3. Viability with niraparib and olaparib in additional clones – related to Figure 2. A) Immunoblotting analysis of POLB from 2 individual clones confirming POLB knockout in BRCA1 mutant MDA-MB-436 (left) and SUM149PT cells (right). Cl#1 of sgIntron and cl#3 of sgPOLB for MDA-MB-436 and cl#1 of sgIntron and cl#1 of sgPOLB for SUM149PT are same as in Fig. 2A. B) Dose response curves of control (cl#1) and POLB knockout (cl#5) derivatives of MDA-MB436 cells treated with niraparib (left) and dose response curves of control (cl#1) and POLB knockout (cl#2) derivatives of SUM149PT cells treated with niraparib (middle) and olaparib (right) for 7 days. Data are represented as mean +SD, N = 3. Statistical significance was derived from nonlinear regression curves of sgIntron vs. sgPOLB (****, P

Figure S3 from CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors

Key Points

Abstract

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