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Pcna

Kısaca: Proliferatif Hücre Çekirdek Antijeni, ya da sık kullanılan adıyla PCNA, is a protein that acts as a processivity factor for DNA polymerase delta 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. ...devamı ☟

Proliferatif Hücre Çekirdek Antijeni, ya da sık kullanılan adıyla PCNA, is a protein that acts as a processivity factor for DNA polymerase delta 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. }} DNA sentezi sırasında çekirdekte gen ekspresyonu PCNA was 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 delta (Pol δ) 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. DNA Onarımındaki İşlevleri Since DNA polymerase delta is involved in resynthesis of excised damaged DNA strands during DNA repair, PCNA is important for both DNA synthesis and DNA repair. PCNA is also involved in the DNA damage tolerance pathway known as post-replication repair (PRR). In PRR, there are two sub-pathways: (1) translesion synthesis, 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. Mono-ubiquitin of lysine number 164 on PCNA activates the translesion synthesis pathway. Extension of this mono-ubiquitin to form a non-canonical lysine-63-linked poly-ubiquitin chain 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. This antagonistic effect occurs because sumoylated PCNA recruits a DNA helicase called Srs2, which has a role in disrupting Rad51 nucleoprotein filaments fundamental for initiation of homologous recombination. PRR is reviewed in Lehmann and Fuchs, 2006 PCNA-bağlayan proteinler 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 detaylar için bakınız Ayrıca bakınız * Transkripsiyon * Ki-67 - hücre çoğalması belirteci

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