Cross-linking experiments performed in the yeast system have shown that within the transcription initiation complex, eight RNA polymerase III subunits can be cross-linked to DNA (Bartholomew et al., 1993). The C34 subunit, which is known to be required specifically for transcription initiation but not elongation (Wang and Roeder, 1997; Werner et al., 1993), maps the furthest upstream of the transcription start site, in close proximity to Brf1-TFIIIB (Bartholomew et al., 1993). Indeed, this subunit interacts with Brf1 (Khoo et al., 1994; Werner et al., 1993). The figure illustrates this and other protein-protein contacts involving RNA polymerase III subunits and either TFIIIC or Brf1-TFIIIB subunits. The contacts identified with S. cerevisiae proteins are indicated by stippled arrows, those identified with human protein by solid arrows. Both the S. cerevisiae RNA polymerase III subunits C53 and ABC10a interact with Tfc4 ( 1999; Flores et al., 1999), and both C17 and C34 interact with Brf1. The human subunit RPC62 interacts with TIIIC63, and RPC39 with the TFIIIC subunits TFIIIC90 and TFIIIC63 (Hsieh et al., 1999a) and the Brf1-TFIIIB subunits Brf1 and TBP (Wang and Roeder, 1997). The contacts between RNA polymerase III and TFIIIC subunits are not absolutely required for transcription in vitro with the S. cerevisiae system, in which TFIIIC can be stripped from the DNA after assembly of TFIIIB without compromising transcription (Kassavetis et al., 1990) or, indeed, where transcription can be performed in the absence of TFIIIC on TATA box-containing promoters (Kassavetis et al., 1995). Nevertheless, they may contribute to the recruitment of RNA polymerase III in vivo.