Selected Articles from This Issue

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...