The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication.

[9] PCNA is also found in archaea, as a processivity factor of polD, the single multi-functional DNA polymerase in this domain of life.

PCNA is clamped[13] to DNA through the action of replication factor C (RFC),[14] which is a heteropentameric member of the AAA+ class of ATPases.

Furthermore, sumoylation (by small ubiquitin-like modifier, SUMO) of PCNA lysine-164 (and to a lesser extent, lysine-127) inhibits the template switch pathway.

[20] This antagonistic effect occurs because sumoylated PCNA recruits a DNA helicase called Srs2,[21] which has a role in disrupting Rad51 nucleoprotein filaments fundamental for initiation of homologous recombination.

Imaging of the nuclear distribution of PCNA (via antibody labeling) can be used to distinguish between early, mid and late S phase of the cell cycle.

[93][94] In 2023 City of Hope National Medical Center published preclinical research on a targeted chemotherapy using AOH1996 that appears to suppress tumor growth without causing discernable side effects.