View source for 8e84


==Human PCNA mutant- C148S==
<StructureSection load='8e84' size='340' side='right'caption='[[8e84]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8e84]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E84 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E84 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8e84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e84 OCA], [https://pdbe.org/8e84 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e84 RCSB], [https://www.ebi.ac.uk/pdbsum/8e84 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e84 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PCNA_HUMAN PCNA_HUMAN] Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.<ref>PMID:19443450</ref> <ref>PMID:18719106</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Proliferating Cell Nuclear Antigen (PCNA) is a sliding clamp protein that coordinates DNA replication with various DNA maintenance events that are critical for human health. Recently, a hypomorphic homozygous serine to isoleucine (S228I) substitution in PCNA was described to underlie a rare DNA repair disorder known as PCNA-Associated DNA Repair Disorder (PARD). PARD symptoms range from UV sensitivity, neurodegeneration, telangiectasia, and premature aging. We, and others, previously showed that the S228I variant changes the protein binding pocket of PCNA to a conformation that impairs interactions with specific partners. Here, we report a second PCNA substitution (C148S) that also causes PARD. Unlike PCNA-S228I, PCNA-C148S has WT-like structure and affinity towards partners. In contrast, both disease-associated variants possess a thermo-stability defect. Furthermore, patient-derived cells homozygous for the C148S allele exhibit low levels of chromatin-bound PCNA and display temperature-dependent phenotypes. The stability defect of both PARD variants indicates that PCNA levels are likely an important driver of PARD disease. These results significantly advance our understanding of PARD and will likely stimulate additional work focused on clinical, diagnostic, and therapeutic aspects of this severe disease.

A thermosensitive PCNA allele underlies an Ataxia Telangiectasia-like disorder.,Magrino J, Munford V, Martins DJ, Homma TK, Page B, Gaubitz C, Freire BL, Lerario AM, Vilar JB, Amorin A, Leao EKE, Kok F, Menck CFM, Jorge AAL, Kelch BA J Biol Chem. 2023 Mar 27:104656. doi: 10.1016/j.jbc.2023.104656. PMID:36990216<ref>PMID:36990216</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8e84" style="background-color:#fffaf0;"></div>

==See Also==
*[[Proliferating cell nuclear antigen 3D structures|Proliferating cell nuclear antigen 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gaubitz C]]
[[Category: Kelch BA]]
[[Category: Magrino J]]
[[Category: Page B]]