Proliferating cell nuclear antigen (PCNA) plays a key role in many cellular processes
and due to that it interacts with a plethora of proteins. The main interacting surfaces
of Saccharomyces cerevisiae PCNA have been mapped to the interdomain connecting loop
and to the carboxy-terminal domain. Here we report that the subunit interface of yeast
PCNA also has regulatory roles in the function of several DNA damage response pathways.
Using sitedirected mutagenesis we engineered mutations at both sides of the interface
and investigated the effect of these alleles on DNA damage response. Genetic experiments
with strains bearing the mutant alleles revealed that mutagenic translesion synthesis,
nucleotide excision repair, and homologous recombination are all regulated through
residues at the subunit interface. Moreover, genetic characterization of one of our
mutants identifies a new sub-branch of nucleotide excision repair. Based on these
results we conclude that residues at the subunit boundary of PCNA are not only important
for the formation of the trimer structure of PCNA, but they constitute a regulatory
protein domain that mediates different DNA damage response pathways, as well.