Proliferating cell nuclear antigen originally identified as an antigen that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle. Part of the protein was sequenced and that sequence was used to allow isolation of a cDNA clone. PCNA helps hold DNA polymerase epsilon (Pol ε) to DNA. PCNA is clamped to DNA through the action of replication factor C (RFC), which is a heteropentameric member of the AAA+ class of ATPases. Expression of PCNA is under the control of E2F transcription factor-containing complexes. Since DNA polymerase epsilon is involved in resynthesis of excised damaged DNA strands during
DNA repair for multiple cell generations, and can be considered to be epimutations (equivalent to mutations). While large numbers of epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, appear to be particularly important. Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability characteristic of cancers. Reduced expression of DNA repair genes causes deficient DNA repair. When DNA repair is deficient DNA damages remain in cells at a higher than usual level and these excess damages cause increased frequencies