(4) Altered DNA repair: Repair mechanisms increased, i.e., ability to remove cross-links Affect the action of bleomycin and other DNA-directed drugs (5) Altered target: Less affinity for drug, Methotrexate Dihydrofolate reductase changes )• (4) Altered DNA repair: Repair mechanisms increased, i.e., ability to remove cross-links, Affect the action of bleomycin and other DNA-directed drugs • (5) Altered target: Less affinity for drug, Methotrexate (Dihydrofolate reductase changes )