PCNA Mouse Monoclonal Antibody [4-E11]

Function

Proliferating cell nuclear antigen (PCNA) is a member of the DNA sliding clamp family of proteins that assist in DNA replication. Crystal structure data suggests that a PCNA homotrimer ring can encircle and slide along the DNA double helix. Multiple proteins involved in DNA replication, DNA repair, and cell cycle control bind to PCNA rather than directly associating with DNA, thus facilitating fast processing of DNA. PCNA protein expression is a well-accepted marker of proliferation.

Background References

1. "Interaction of human DNA polymerase eta with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage." Kannouche P.L., Wing J., Lehmann A.R. Mol. Cell 14:491-500(2004).

2. "Tyrosine phosphorylation controls PCNA function through protein stability." Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C. Nat. Cell Biol. 8:1359-1368(2006).

Sequence Similarity

Belongs to the PCNA family.

Post-translational Modification

Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA.; Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation. Lysine acetylation disrupts association with chromatin, hence promoting PCNA ubiquitination and proteasomal degradation in response to UV damage in a CREBBP- and EP300-dependent manner. Acetylation disrupts interaction with NUDT15 and promotes degradation.; Ubiquitinated. Following DNA damage, can be either monoubiquitinated to stimulate direct bypass of DNA lesions by specialized DNA polymerases or polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Following induction of replication stress, monoubiquitinated by the UBE2B-RAD18 complex on Lys-164, leading to recruit translesion (TLS) polymerases, which are able to synthesize across DNA lesions in a potentially error-prone manner. An error-free pathway also exists and requires non-canonical polyubiquitination on Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH. This error-free pathway, also known as template switching, employs recombination mechanisms to synthesize across the lesion, using as a template the undamaged, newly synthesized strand of the sister chromatid. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis. Sumoylated during S phase.; Methylated on glutamate residues by ARMT1/C6orf211.

Subcellular Location

Nucleus

UNIPROT

SwissProt: P12004 Human

Synonyms