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 daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). This can eventually lead to malignant tumors, or cancer as per the two hit hypothesis. The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA