Abstract: An isolated nucleic acid is provided, which encodes a stress-responsive subunit of mammalian RNA polymerase II, RPB4. In a preferred embodiment, the human RPB4 subunit (hsRPB4) is provided. Also provided are oligonucleotides that specifically hybridize with the nucleic acid, the purified polypeptide encoded by the nucleic acid and antibodies immunologically specific for the polypeptide. These biological molecules are useful as markers of stress-related responses, which may correspond to the occurrence of malignant disease, and as therapeutic agents to modify resistance of a selected cell population to external stress conditions, such as that resulting from treatment of a patient with chemotherapeutic agents.