21:T4f1,Sulfolobus islandicus codes for four DNA polymerases: three are of the B-family (Dpo1, Dpo2, and Dpo3), and one is of the Y-family (Dpo4). Western analysis revealed that among the four polymerases, only Dpo2 exhibited DNA damage-inducible expression. To investigate how these DNA polymerases could contribute to DNA damage tolerance in S. islandicus, we conducted genetic analysis of their encoding genes in this archaeon. Plasmid-borne gene expression revealed that Dpo2 increases cell survival upon DNA damage at the expense of mutagenesis. Gene deletion studies showed although dpo1 is essential, the remaining three genes are dispensable. Furthermore, although Dpo4 functions in housekeeping translesion DNA synthesis (TLS), Dpo2, a B-family DNA polymerase once predicted to be inactive, functions as a damage-inducible TLS enzyme solely responsible for targeted mutagenesis, facilitating GC to AT/TA conversions in the process. Together, our data indicate that Dpo2 is the main DNA polymerase responsible for DNA damage tolerance and is the primary source of targeted mutagenesis. Given that crenarchaea encoding a Dpo2 also have a low-GC composition genome, the Dpo2-dependent DNA repair pathway may be conserved in this archaeal lineage.22:T450,Current chemotherapeutic agents against esophageal cancer (EC) are suboptimal. To improve treatment efficacy, a nanoplatform based on ATP-responsive drug release was developed for EC therapy. First, the chemotherapeutic agent epirubicin (EPI) was inserted into an ATP aptamer (Ap) to form double-stranded DNA ('DNA duplex'). Subsequently, polyethyleneimine (PEI) was employed to condense the EPI-loaded duplex to construct the final nanoplatform (PEI-Ap-EPI). Following internalization by cancer cells, the EPI-loaded DNA duplex could open and release EPI in an intracellular ATP-rich environment. An in vitro drug-release assay demonstrated that ~50% of EPI was released from PEI-Ap-EPI in an ATP-rich condition. However, only 15% of EPI was released in the presence of a low concentration of ATP. In vitro cytotoxicity and apoptosis assays demonstrated that PEI-Ap-EPI could enhance EPI efficiency against EC cells markedly compared with those in the control group. Therefore, this facile PEI-Ap-EPI nanoplatform may be a promising strategy to improve the efficacy of EPI treatment in EC.

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