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- W3093588967 abstract "DNA damage response (DDR) pathways could preserve genome stability. Mediator of DNA damage checkpoint protein 1 (MDC1) plays a critical role in the DDR machinery by interacting directly with several factors, such as γH2AX via phosphorylating H2AX at DNA damage sites. However, the mechanism by which MDC1 is recruited to DNA damaged sites still remains prevalently elusive. Cancer cells were cultured in DMEM or RPMI-1640 medium with 10% FBS in a humidified atmosphere containing 5% CO2 at 37°C. Interaction between MDC1 and ubiquitin-specific peptidase 39 (USP39) was examined with co-immunoprecipitation, western blot, immunofluorescence, proximity ligation assay. homologous recombination (HR) repair and non-homology end joining (NHEJ) efficiency was detected by flow cytometry. DNA damages were induced by ionizing radiation (IR) and examined with western blot and immunofluorescence. We identify a highly conserved protein USP39 that could be interacted with MDC1 and recruitment to DNA damage sites. Moreover, knockdown of USP39 results in impaired formation of IR-induced γH2AX foci and MDC1 foci, impaired both HR repair and NHEJ repair, promoted radiosensitivity and genomic instability. In summary, we reveal a previously unknown interaction between MDC1 and USP39 and imply USP39 as a novel regulator of MDC1 in facilitating DDR and maintaining genome stability." @default.
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- W3093588967 date "2020-11-01" @default.
- W3093588967 modified "2023-09-26" @default.
- W3093588967 title "MDC1 Interacts with USP39 to Maintain Genome Stability And Promote DDR" @default.
- W3093588967 doi "https://doi.org/10.1016/j.ijrobp.2020.07.1638" @default.
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