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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/15 17:09:23」(JST)

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Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase ε in eukaryotic cells. It achieves this processivity by encircling the DNA, thus creating a topological link to the genome. It is an example of a DNA clamp.

The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome.^[1]

Expression in the nucleus during DNA synthesis[edit]

PCNA was originally identified as an antigen that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle.^[2] Part of the protein was sequenced and that sequence was used to allow isolation of a cDNA clone.^[3] PCNA helps hold DNA polymerase epsilon (Pol ε) to DNA. PCNA is clamped^[4] to DNA through the action of replication factor C (RFC),^[5] which is a heteropentameric member of the AAA+ class of ATPases. Expression of PCNA is under the control of E2F transcription factor-containing complexes.^[6]

Role in DNA repair[edit]

Since DNA polymerase epsilon is involved in resynthesis of excised damaged DNA strands during DNA repair, PCNA is important for both DNA synthesis and DNA repair.^[7]^[8]

PCNA is also involved in the DNA damage tolerance pathway known as post-replication repair (PRR).^[9] In PRR, there are two sub-pathways: (1) a translesion pathway, which is carried out by specialised DNA polymerases that are able to incorporate damaged DNA bases into their active sites (unlike the normal replicative polymerase, which stall), and hence bypass the damage, and (2) a proposed "template switch" pathway that is thought to involve damage bypass by recruitment of the homologous recombination machinery. PCNA is pivotal to the activation of these pathways and the choice as to which pathway is utilised by the cell. PCNA becomes post-translationally modified by ubiquitin.^[10] Mono-ubiquitin of lysine number 164 on PCNA activates the translesion synthesis pathway. Extension of this mono-ubiquitin by a non-canonical lysine-63-linked poly-ubiquitin chain on PCNA^[10] is thought to activate the template switch pathway. Furthermore, sumoylation (by small ubiquitin-like modifier, SUMO) of PCNA lysine-164 (and to a lesser extent, lysine-127) inhibits the template switch pathway.^[10] This antagonistic effect occurs because sumoylated PCNA recruits a DNA helicase called Srs2,^[11] which has a role in disrupting Rad51 nucleoprotein filaments fundamental for initiation of homologous recombination.

PCNA-binding proteins[edit]

• TCP protein domain • NKp44 Receptor, DNA polymerases • Clamp loader • Flap endonuclease • DNA ligase • Topoisomerase • Replication licensing factor • E3 ubiquitin ligases • E2 SUMO-conjugating enzyme • Helicases, ATPases • Mismatch repair enzymes • Base excision repair enzymes • Nucleotide excision repair enzyme • Poly ADP ribose polymerase • Histone chaperone • Chromatin remodeling factor • Histone acetyltransferase • Histone deacetyltransferase • DNA methyltransferase • Sister-chromatid cohesion factors • Protein kinases • Cell-cycle regulators • Apoptotic factors

for details see^[12]

Interactions[edit]

PCNA has been shown to interact with Ku70,^[13]^[14] MSH3,^[13]^[15]^[16] Werner syndrome ATP-dependent helicase,^[17]^[18] RFC2,^[13]^[19]^[20] RFC3,^[13]^[21] RFC1,^[13]^[22]^[23]^[24]^[25] RFC4,^[13]^[19] RFC5,^[13]^[19]^[24] GADD45G,^[26]^[27] CDC25C,^[28] MUTYH,^[29] Flap structure-specific endonuclease 1,^[30]^[31]^[32]^[33]^[34]^[35]^[36] Cyclin O,^[13]^[37] CHTF18,^[13] Y box binding protein 1,^[38] Cyclin D1,^[39]^[40] Annexin A2,^[13] MSH6,^[13]^[15]^[16] DNMT1,^[41]^[42]^[43] HDAC1,^[44] KCTD13,^[45] XRCC1,^[46] Cyclin-dependent kinase 4,^[40]^[47] Ku80,^[13]^[14]^[48] HUS1,^[49] GADD45A,^[50]^[51]^[52]^[53]^[54] POLD2,^[55] ING1,^[56] POLH,^[57] KIAA0101,^[36] POLDIP2,^[58] EP300,^[59] MCL1,^[60] POLD3,^[13]^[61] Cyclin-dependent kinase inhibitor 1C,^[62] POLL,^[63]^[64]^[65] Ubiquitin C^[66]^[67]^[68] and P21.^[23]^[32]^[36]^[62]^[69]^[70]^[71]^[72]

Uses[edit]

Antibodies against proliferating cell nuclear antigen (PCNA) or monoclonal antibody termed Ki-67 can be used for grading of different neoplasms, e.g. astrocytoma. They can be of diagnostic and prognostic value.

External links[edit]

PCNA at the US National Library of Medicine Medical Subject Headings (MeSH)
"ANA: Cell cycle related (Mitotic): PCNA type 1 and type 2 Antibody Patterns". Antibody Patterns.com. Retrieved 2008-04-15.
Dan Krotz. "Structure of a clamp–loader complex". Advanced Light Source News. Lawrence Berkeley National Laboratory. Retrieved 2008-04-15. ^[4]
"Movie showing a model of clamp loading of PCNA onto DNA". Pubmed Central. ^[73]

References[edit]

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English Journal

Silver nanoparticles induce toxicity in A549 cells via ROS-dependent and ROS-independent pathways.

Chairuangkitti P, Lawanprasert S, Roytrakul S, Aueviriyavit S, Phummiratch D, Kulthong K, Chanvorachote P, Maniratanachote R.SourceFaculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Rd., Pathumwan, Bangkok 10330, Thailand.
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Silver nanoparticles (AgNPs) are incorporated into a large number of consumer and medical products. Several experiments have demonstrated that AgNPs can be toxic to the vital organs of humans and especially to the lung. The present study evaluated the in vitro mechanisms of AgNP (<100nm) toxicity
PMID 22940466

Apigenin prevents deregulation in the expression pattern of cell-proliferative, apoptotic, inflammatory and angiogenic markers during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

Silvan S, Manoharan S.SourceDepartment of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu 608 002, India.
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OBJECTIVE: Malignant tumour arises due to abnormal cell proliferation, chronic inflammation, defect in apoptotic pathway and unwanted angiogenesis. The present study has investigated the modulating effect of apigenin on expression pattern of apoptotic (p53, Bcl-2, Bax, Caspase-3 and 9) cell prolifer
PMID 22776109

Japanese Journal

Roadworks of DNA Damage Bypass during and after Replication

DAIGAKU Yasukazu
Genes and environment : the official journal of the Japanese Environmental Mutagen Society 34(2), 77-88, 2012-05-20
NAID 10030311548

In Vitro Studies of Exchanges between Replicative and Translesion DNA Polymerases in the Eukaryotic Post-replication Repair Pathway

MASUDA Yuji
Genes and environment : the official journal of the Japanese Environmental Mutagen Society 34(2), 70-76, 2012-05-20
NAID 10030311492

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★リンクテーブル★

リンク元	「増殖性細胞核抗原」「増殖細胞核抗原」
関連記事	「PC」

「増殖性細胞核抗原」

Proliferating cell nuclear antigen
	; The assembled human DNA clamp, a trimer of the protein PCNA.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1AXC, 1U76, 1U7B, 1UL1, 1VYJ, 1VYM, 1W60, 2ZVK, 2ZVL, 2ZVM, 3P87, 3TBL, 3VKX
Identifiers
Symbols	PCNA; MGC8367
External IDs	OMIM: 176740 MGI: 97503 HomoloGene: 1945 GeneCards: PCNA Gene
Gene Ontology
Molecular function	• purine-specific mismatch base pair DNA N-glycosylase activity; • protein binding; • DNA polymerase processivity factor activity; • receptor tyrosine kinase binding; • dinucleotide insertion or deletion binding; • MutLalpha complex binding; • identical protein binding;
Cellular component	• nucleus; • nucleoplasm; • DNA replication factor C complex; • nucleolus; • cytoplasm; • microtubule cytoskeleton; • nuclear replication fork; • PCNA complex; • PCNA-p21 complex;
Biological process	• G1/S transition of mitotic cell cycle; • regulation of transcription involved in G1/S phase of mitotic cell cycle; • S phase of mitotic cell cycle; • mitotic cell cycle; • telomere maintenance via recombination; • telomere maintenance; • DNA replication; • DNA strand elongation involved in DNA replication; • regulation of DNA replication; • DNA repair; • transcription-coupled nucleotide-excision repair; • base-excision repair; • nucleotide-excision repair; • nucleotide-excision repair, DNA gap filling; • mismatch repair; • heart development; • cell proliferation; • translesion synthesis; • positive regulation of deoxyribonuclease activity; • telomere maintenance via semi-conservative replication; • response to lipid; • response to cadmium ion; • phosphatidylinositol-mediated signaling;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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　　[★]

英: proliferating cell nuclear antigen、PCNA

「増殖細胞核抗原」

　　[★]

英: [[]]
同: PCNA
関: [[]]

同: PCNA

「PC」

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[entrez-1] "Entrez Gene: PCNA proliferating cell nuclear antigen".

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[pmid12192049-22] Maruyama, Tetsuo; Farina Andrea, Dey Anup, Cheong JaeHun, Bermudez Vladimir P, Tamura Tomohiko, Sciortino Selvaggia, Shuman Jon, Hurwitz Jerard, Ozato Keiko (September 2002). "A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase". Mol. Cell. Biol. (United States) 22 (18): 6509–6520. doi:10.1128/MCB.22.18.6509-6520.2002. ISSN 0270-7306. PMC 135621. PMID 12192049.

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[pmid10353443-25] van der Kuip, H; Carius B, Haque S J, Williams B R, Huber C, Fischer T (April 1999). "The DNA-binding subunit p140 of replication factor C is upregulated in cycling cells and associates with G1 phase cell cycle regulatory proteins". J. Mol. Med. (GERMANY) 77 (4): 386–392. doi:10.1007/s001090050365. ISSN 0946-2716. PMID 10353443.

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