8d0k: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8d0k]] is a 8 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=8D0K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D0K FirstGlance]. <br>
<table><tr><td colspan='2'>[[8d0k]] is a 8 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=8D0K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D0K FirstGlance]. <br>
</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=8d0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d0k OCA], [https://pdbe.org/8d0k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d0k RCSB], [https://www.ebi.ac.uk/pdbsum/8d0k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d0k ProSAT]</span></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]] 4.27&#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=8d0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d0k OCA], [https://pdbe.org/8d0k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d0k RCSB], [https://www.ebi.ac.uk/pdbsum/8d0k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d0k ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://www.uniprot.org/uniprot/CTC1_HUMAN CTC1_HUMAN]] Coats plus syndrome;Dyskeratosis congenita. The disease is caused by mutations affecting the gene represented in this entry.
[https://www.uniprot.org/uniprot/CTC1_HUMAN CTC1_HUMAN] Coats plus syndrome;Dyskeratosis congenita. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/CTC1_HUMAN CTC1_HUMAN]] Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Involved in telomere maintenance (PubMed:19854131, PubMed:22863775). Involved in genome stability (PubMed:22863775). May be in involved in telomeric C-strand fill-in during late S/G2 phase (By similarity).[UniProtKB:Q5SUQ9]<ref>PMID:19854130</ref> <ref>PMID:19854131</ref> <ref>PMID:22763445</ref> <ref>PMID:22863775</ref> <ref>PMID:25483097</ref>  
[https://www.uniprot.org/uniprot/CTC1_HUMAN CTC1_HUMAN] Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Involved in telomere maintenance (PubMed:19854131, PubMed:22863775). Involved in genome stability (PubMed:22863775). May be in involved in telomeric C-strand fill-in during late S/G2 phase (By similarity).[UniProtKB:Q5SUQ9]<ref>PMID:19854130</ref> <ref>PMID:19854131</ref> <ref>PMID:22763445</ref> <ref>PMID:22863775</ref> <ref>PMID:25483097</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The mammalian DNA polymerase-alpha-primase (Polalpha-primase) complex is essential for DNA metabolism, providing the de novo RNA-DNA primer for several DNA replication pathways(1-4) such as lagging-strand synthesis and telomere C-strand fill-in. The physical mechanism underlying how Polalpha-primase, alone or in partnership with accessory proteins, performs its complicated multistep primer synthesis function is unknown. Here we show that CST, a single-stranded DNA-binding accessory protein complex for Polalpha-primase, physically organizes the enzyme for efficient primer synthesis. Cryogenic electron microscopy structures of the CST-Polalpha-primase preinitiation complex (PIC) bound to various types of telomere overhang reveal that template-bound CST partitions the DNA and RNA catalytic centres of Polalpha-primase into two separate domains and effectively arranges them in RNA-DNA synthesis order. The architecture of the PIC provides a single solution for the multiple structural requirements for the synthesis of RNA-DNA primers by Polalpha-primase. Several insights into the template-binding specificity of CST, template requirement for assembly of the CST-Polalpha-primase PIC and activation are also revealed in this study.


Structures of the human CST-Polalpha-primase complex bound to telomere templates.,He Q, Lin X, Chavez BL, Agrawal S, Lusk BL, Lim CJ Nature. 2022 Aug;608(7924):826-832. doi: 10.1038/s41586-022-05040-1. Epub 2022, Jul 13. PMID:35830881<ref>PMID:35830881</ref>
==See Also==
 
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8d0k" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 12:40, 14 February 2024

Human CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback template - PRIM2C advanced PICHuman CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback template - PRIM2C advanced PIC

Structural highlights

8d0k is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 4.27Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CTC1_HUMAN Coats plus syndrome;Dyskeratosis congenita. The disease is caused by mutations affecting the gene represented in this entry.

Function

CTC1_HUMAN Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Involved in telomere maintenance (PubMed:19854131, PubMed:22863775). Involved in genome stability (PubMed:22863775). May be in involved in telomeric C-strand fill-in during late S/G2 phase (By similarity).[UniProtKB:Q5SUQ9][1] [2] [3] [4] [5]

See Also

References

  1. ↑ Miyake Y, Nakamura M, Nabetani A, Shimamura S, Tamura M, Yonehara S, Saito M, Ishikawa F. RPA-like mammalian Ctc1-Stn1-Ten1 complex binds to single-stranded DNA and protects telomeres independently of the Pot1 pathway. Mol Cell. 2009 Oct 23;36(2):193-206. PMID:19854130 doi:S1097-2765(09)00587-5
  2. ↑ Surovtseva YV, Churikov D, Boltz KA, Song X, Lamb JC, Warrington R, Leehy K, Heacock M, Price CM, Shippen DE. Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. Mol Cell. 2009 Oct 23;36(2):207-18. PMID:19854131 doi:http://dx.doi.org/S1097-2765(09)00675-3
  3. ↑ Chen LY, Redon S, Lingner J. The human CST complex is a terminator of telomerase activity. Nature. 2012 Aug 23;488(7412):540-4. doi: 10.1038/nature11269. PMID:22763445 doi:http://dx.doi.org/10.1038/nature11269
  4. ↑ Stewart JA, Wang F, Chaiken MF, Kasbek C, Chastain PD 2nd, Wright WE, Price CM. Human CST promotes telomere duplex replication and general replication restart after fork stalling. EMBO J. 2012 Aug 29;31(17):3537-49. doi: 10.1038/emboj.2012.215. Epub 2012 Aug 3. PMID:22863775 doi:http://dx.doi.org/10.1038/emboj.2012.215
  5. ↑ Wang F, Stewart J, Price CM. Human CST abundance determines recovery from diverse forms of DNA damage and replication stress. Cell Cycle. 2014;13(22):3488-98. doi: 10.4161/15384101.2014.964100. PMID:25483097 doi:http://dx.doi.org/10.4161/15384101.2014.964100

8d0k, resolution 4.27Å

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