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ATR

Control of Replication Stress and Mitosis in Colorectal Cancer Stem Cells through the Interplay of PARP1, MRE11 and RAD51

[Cell Death & Differentiation] Researchers showed that the replication stress response was efficient in primary CSCs from colorectal cancer, and described unique roles for PARP1 and MRE11/RAD51.

DNA Damage in Human Glomerular Endothelial Cells Induces Nodular Glomerulosclerosis via an ATR and ANXA2 Pathway

[Scientific Reports] In in vitro studies, collagen type VI secretion from human renal glomerular endothelial cells was assessed by measuring the decrease in the cytoplasmic COL6-positive cells and an increase in the amount of COL6 in the culture medium.

Non-Epigenetic Induction of HEXIM1 by DNMT1 Inhibitors and Functional Relevance

[Scientific Reports] 5-AzadC induced HEXIM1 expression in prostate cancer cell lines and triple negative breast cancers. 5-AzadC-induced DNA damage enhanced P-TEFb occupancy via a mechanism that involved activation of ATR and ATM and induction of NF-ĸB recruitment to the HEXIM1 promoter.

AXL Inhibition Induces DNA Damage and Replication Stress in Non-Small Cell Lung Cancer Cells and Promotes Sensitivity to ATR Inhibitors

[Molecular Cancer Research] Researchers showed that BGB324, a selective small-molecule AXL inhibitor, caused DNA damage and induced replication stress, indicated by ATR/CHK1 phosphorylation, more significantly in TP53-deficient non-small cell lung cancer cell lines.

The POLD1R689W Variant Increases the Sensitivity of Colorectal Cancer Cells to ATR and CHK1 Inhibitors

[Scientific Reports] Using CRISPR/Cas9 in the colorectal cancer cell line DLD-1, which harbors four POLD1 variants, scientists established heterozygous POLD1-knockout clones with exclusive expression of distinct variants to determine the functional relevance of these variants individually by assessing their impact on ATR pathway activation, DNA replication, and cellular sensitivity to inhibition of ATR or its effector kinase CHK1.

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

[Gastroenterology] Scientists interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel pancreatic cancer patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids.

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