Methods of specifically capturing and processing nucleic acids from samples in a simplified, streamlined workflow. Media conditions and/or workflow improvements provided herein permit workflow steps such as cell lysis, nucleic acid denaturation, and target nucleic acid capture and immobilization to be performed in a “one-pot” reaction with minimal or no subsequent washing or rinsing steps prior to enzymatic processing. The media conditions include particular salt and/or detergent concentrations, and the workflow improvements include improved purification steps. The media conditions and workflow improvements effectively isolate target nucleic acid for downstream enzymatic processing reactions while avoiding levels of contaminants that inhibit such reactions.