6tny: Difference between revisions

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<SX load='6tny' size='340' side='right' viewer='molstar' caption='[[6tny]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
<SX load='6tny' size='340' side='right' viewer='molstar' caption='[[6tny]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6tny]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TNY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TNY FirstGlance]. <br>
<table><tr><td colspan='2'>[[6tny]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TNY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TNY FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.08&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=TTP:THYMIDINE-5-TRIPHOSPHATE'>TTP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POLD1, POLD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), POLD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), POLD3, KIAA0039 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), POLD4, POLDS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PCNA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6tny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tny OCA], [https://pdbe.org/6tny PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tny RCSB], [https://www.ebi.ac.uk/pdbsum/6tny PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tny ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tny OCA], [http://pdbe.org/6tny PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tny RCSB], [http://www.ebi.ac.uk/pdbsum/6tny PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tny ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/DPOD1_HUMAN DPOD1_HUMAN]] Mandibular hypoplasia-deafness-progeroid features-lipodystrophy syndrome;Polymerase proofreading-related adenomatous polyposis. Disease susceptibility is associated with variations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  
[https://www.uniprot.org/uniprot/DPOD1_HUMAN DPOD1_HUMAN] Mandibular hypoplasia-deafness-progeroid features-lipodystrophy syndrome;Polymerase proofreading-related adenomatous polyposis. Disease susceptibility is associated with variations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/DPOD4_HUMAN DPOD4_HUMAN]] As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity (PubMed:16510448, PubMed:19074196, PubMed:20334433). Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system (PubMed:24035200). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb (PubMed:24310611). Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival (PubMed:24022480).<ref>PMID:16510448</ref> <ref>PMID:19074196</ref> <ref>PMID:20334433</ref> <ref>PMID:24022480</ref> <ref>PMID:24035200</ref> <ref>PMID:24310611</ref>  [[http://www.uniprot.org/uniprot/DPOD1_HUMAN DPOD1_HUMAN]] As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200, PubMed:24022480). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196).<ref>PMID:16510448</ref> <ref>PMID:19074196</ref> <ref>PMID:20227374</ref> <ref>PMID:20334433</ref> <ref>PMID:24022480</ref> <ref>PMID:24035200</ref> <ref>PMID:24310611</ref> [[http://www.uniprot.org/uniprot/DPOD3_HUMAN DPOD3_HUMAN]] Required for optimal DNA polymerase delta activity.<ref>PMID:10219083</ref> <ref>PMID:10852724</ref> <ref>PMID:16510448</ref>  [[http://www.uniprot.org/uniprot/DPOD2_HUMAN DPOD2_HUMAN]] The function of the small subunit is not yet clear. [[http://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> 
[https://www.uniprot.org/uniprot/DPOD1_HUMAN DPOD1_HUMAN] As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200, PubMed:24022480). Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196).<ref>PMID:16510448</ref> <ref>PMID:19074196</ref> <ref>PMID:20227374</ref> <ref>PMID:20334433</ref> <ref>PMID:24022480</ref> <ref>PMID:24035200</ref> <ref>PMID:24310611</ref>  
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
*[[Proliferating cell nuclear antigen 3D structures|Proliferating cell nuclear antigen 3D structures]]
== References ==
== References ==
<references/>
<references/>
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[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Biasio, A De]]
[[Category: Synthetic construct]]
[[Category: Hamdan, S M]]
[[Category: De Biasio A]]
[[Category: Lancey, C]]
[[Category: Hamdan SM]]
[[Category: Protein]]
[[Category: Lancey C]]
[[Category: Replication]]

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