Ataxia telangiectasia mutated (ATM) orchestrates DNA double-strand break (DSB) responses by phosphorylating proteins that regulate DNA damage repair (DDR). ATM mutations potentiate oncogenic transformation and characterizing the ATM interactome may unveil novel mechanisms underlying DDR and carcinogenesis. Using proteomic screens, Bass and colleagues discovered novel interactions between ATM and cohesin complex constituents, including PDS5A. The authors confirmed that ATM phosphorylates PDS5A using a pharmacologic ATM inhibitor and Western blotting. Moreover, they found that phosphomutant PDS5A transfection increases irradiation-induced DNA damage, suggesting ATM-mediated PDS5A phosphorylation promotes DDR. Using a reporter cell line in which DSB and DDR-induced transcription repression can be tracked using red and yellow fluorescence, respectively, the authors showed that ATM-mediated PDS5A phosphorylation facilitates transcription repression in response to DSBs. The authors also developed a novel S-phase checkpoint assay capable of measuring 5-ethynyl-2’-deoxyuridine (EdU) incorporation in the vicinity of fluorescent DSB radii and showed that PDS5A phosphorylation slows DNA...
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Highlights| March 01 2023
Selected Articles from This Issue
Online ISSN: 1557-3125
Print ISSN: 1541-7786
©2023 American Association for Cancer Research
American Association for Cancer Research
Mol Cancer Res (2023) 21 (3): 187.
A commentary has been published: Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells
A commentary has been published: A Novel Tumor-Promoting Role for Nuclear Factor IX in Glioblastoma Is Mediated through Transcriptional Activation of GINS1
A commentary has been published: ATM Regulation of the Cohesin Complex Is Required for Repression of DNA Replication and Transcription in the Vicinity of DNA Double-Strand Breaks
A commentary has been published: MUC1-C Dictates PBRM1-Mediated Chronic Induction of Interferon Signaling, DNA Damage Resistance, and Immunosuppression in Triple-Negative Breast Cancer
Selected Articles from This Issue. Mol Cancer Res 1 March 2023; 21 (3): 187. https://doi.org/10.1158/1541-7786.MCR-21-3-HI
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