PROLIFERATING CELL NUCLEAR ANTIGEN (POL30) MUTATIONS SUPPRESS CDC44 MUTATIONS AND IDENTIFY POTENTIAL REGIONS OF INTERACTION BETWEEN THE 2 ENCODED PROTEINS

In addition to its role as a processivity factor in DNA replication, proliferating cell nuclear antigen (PCNA) may function in the regulation of cell cycle progression. We present genetic evidence that PCNA interacts; with the gene product of CDC44, an essential nucleotide-binding protein that encodes the large subunit of yeast replication factor C (K. Fien and B. Stillman, personal communication). Mutations in POL30 (PCNA) suppress cold-sensitive alleles of cdc44 that contain mutations in or near nucleotide-binding consensus domains, but they do not suppress a null allele. Thus, it appears that PCNA interacts with Cdc44p but cannot substitute for its function. pol30 mutations suppress additional phenotypes of cdc44 mutations, including the cold sensitivity that they were selected to suppress. This observation suggests an intimate association between PCNA and Cdc44p. Each of five independent pol30 mutants contains a unique single mutation that maps to a localized region on one face of the predicted three-dimensional structure of PCNA. This face identifies a region likely to be important for functional interaction between the CDC44 and POL30 gene products.