ArticlebioRxiv : the preprint server for biology2026
Viral rewiring of DDR signaling activates a pro-survival network that drives chemotherapy resistance.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
Funding
Abstract
Radiation and chemotherapy rely on an intact DNA damage response (DDR) to halt cell-cycle progression and eliminate damaged cells, yet many tumors evade these outcomes and develop resistance. Adenoviruses remodel host signaling networks in ways that mirror tumor evolution, providing a powerful system to dissect how DDR pathways are subverted. Here, we identify two scenarios in which the central DDR kinases ATM and ATR are reprogrammed from enforcing CHK1/CHK2-dependent checkpoint arrest to activating a NEMO-NF-κB survival pathway. This rewiring induces transcriptional programs associated with stress tolerance, anti-apoptotic signaling, and chemoresistance, and promotes the accumulation of cells with abnormal DNA content. These findings reveal a previously unrecognized mode of DDR plasticity that generates a pro-survival state reminiscent of early tumor evolution and suggest how ATM- and ATR-dependent pathways can be co-opted to promote therapeutic resistance.
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