Telomere maintenance is a hallmark of malignant cells and allows cancers to divide indefinitely. Together, these data indicate that inhibitors of PARP1 and PARP2 may be clinically relevant for RB-deficient cancers. We demonstrate this sensitivity is conserved across a panel of inhibitors that target both PARP1 and PARP2 and can be suppressed by re-expression of the RB protein. ![]() These defects contribute to high levels of DNA damage, decreased proliferation, and compromised cell viability. We found that loss of RB alone leads to high levels of replication-dependent poly-ADP ribosylation (PARylation) and that preventing PARylation through inhibition of PARP enzymes enables RB-deficient cells to progress to mitosis with unresolved replication stress and under-replicated DNA. To better understand how disruption of RB function impacts epigenetic regulation of genome stability and determine whether such changes may represent exploitable weaknesses of RB-deficient cancer cells, we performed an imaging-based screen to identify epigenetic inhibitors that promote DNA damage and compromise viability of RB-deficient cells. The retinoblastoma tumor suppressor protein (RB) interacts physically and functionally with a number of epigenetic modifying enzymes to control transcriptional regulation, respond to replication stress, promote DNA damage response and repair pathways, and regulate genome stability. This release will ensure that researchers will have continued access to CellProfiler’s powerful computational tools in the coming years. We also evaluated performance and made targeted optimizations to reduce the time and cost associated with running common large-scale analysis pipelines.ĬellProfiler 4 provides significantly improved performance in complex workflows compared to previous versions. We introduced new modules to expand the capabilities of the software. ![]() Based on user feedback, we have made several user interface refinements to improve the usability of the software. ![]() Herein we describe CellProfiler 4, a new version of this software with expanded functionality. CellProfiler is a free, open source image analysis program which enables researchers to generate modular pipelines with which to process microscopy images into interpretable measurements. With the expansion of high throughput microscopy methodologies producing increasingly large datasets, automated and objective analysis of the resulting images is essential to effectively extract biological information from this data. Imaging data contains a substantial amount of information which can be difficult to evaluate by eye.
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