RPB1, the largest subunit (192kDa), is also the largest of all polypeptides associated with any form of the nuclear RNA polymerases. It is involved in nonselective and promoter-dependent transcription. It binds the DNA template and nascent RNA chain and plays a functional role in chain elongation. Experiments that determined the role of RPB1 in DNA binding include UV-crosslinking experiments, inhibition by antibodies and a change in protease susceptibility. Also, genetic deletion experiments were done to determine the viability of the enzyme without the subunit. UV-crossliniking experiments were used to determine its binding to the nascent RNA chain. Its carboxyl terminal domain is modified by phosphorylation, which converts the transcription complex into elongation mode as opposed to the non-phosphorylated (initiation) mode. RPB1 is highly susceptible to proteolysis and is the most sensitive of the nuclear polymerases to alpha-amanitin. The role of RPB1 in chain elongation was determined by mutating its gene, which conferred resistance of alpha-amanitin to the enzyme. The carboxyl-terminal domain characteristically contains the conserved hydrophilic heptapeptide repeat. The yeast enzyme contains 26 copies of this heptapeptide repeat (Carey et al 2000). This part of the enzyme forms about 10-20% of the subunit mass. Its carboxyl terminal domain is modified by phosphorylation, which converts the transcription complex into elongation mode as opposed to the non-phosphorylated (binding) mode. The repeating set of polypeptides also probably confers a flexible secondary structure to the enzyme. With its hydrophilic content, it has been suggested that the carboxyl terminal domain is fully exposed to the solvent at the surface of the enzyme. These properties of the enzyme may be the reason that makes the enzyme susceptible to proteolysis.