5l2x: Difference between revisions

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/PRIPO_HUMAN PRIPO_HUMAN] DNA primase and DNA polymerase able to initiate de novo DNA synthesis using dNTPs. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Involved in translesion synthesis via its primase activity by mediating uninterrupted fork progression after programmed or damage-induced fork arrest and by reinitiating DNA synthesis after dNTP depletion. Required for mitochondrial DNA (mtDNA) synthesis, suggesting it may be involved in DNA tolerance during the replication of mitochondrial DNA. Has non-overlapping function with POLH.<ref>PMID:24126761</ref> <ref>PMID:24207056</ref> <ref>PMID:24240614</ref> <ref>PMID:24267451</ref>  
[https://www.uniprot.org/uniprot/PRIPO_HUMAN PRIPO_HUMAN] DNA primase and DNA polymerase able to initiate de novo DNA synthesis using dNTPs. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Involved in translesion synthesis via its primase activity by mediating uninterrupted fork progression after programmed or damage-induced fork arrest and by reinitiating DNA synthesis after dNTP depletion. Required for mitochondrial DNA (mtDNA) synthesis, suggesting it may be involved in DNA tolerance during the replication of mitochondrial DNA. Has non-overlapping function with POLH.<ref>PMID:24126761</ref> <ref>PMID:24207056</ref> <ref>PMID:24240614</ref> <ref>PMID:24267451</ref>  
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== Publication Abstract from PubMed ==
PrimPol is a novel human enzyme that contains both DNA primase and DNA polymerase activities. We present the first structure of human PrimPol in ternary complex with a DNA template-primer and an incoming deoxynucleoside triphosphate (dNTP). The ability of PrimPol to function as a DNA primase stems from a simple but remarkable feature-almost complete lack of contacts to the DNA primer strand. This, in turn, allows two dNTPs to bind initiation and elongation sites on the enzyme for the formation of the first dinucleotide. PrimPol shows the ability to synthesize DNA opposite ultraviolet (UV) lesions; however, unexpectedly, the active-site cleft of the enzyme is constrained, which precludes the bypass of UV-induced DNA lesions by conventional translesion synthesis. Together, the structure addresses long-standing questions about how DNA primases actually initiate synthesis and how primase and polymerase activities combine in a single enzyme to carry out DNA synthesis.
Structure and mechanism of human PrimPol, a DNA polymerase with primase activity.,Rechkoblit O, Gupta YK, Malik R, Rajashankar KR, Johnson RE, Prakash L, Prakash S, Aggarwal AK Sci Adv. 2016 Oct 21;2(10):e1601317. eCollection 2016 Oct. PMID:27819052<ref>PMID:27819052</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
== References ==
<references/>
<references/>

Latest revision as of 15:43, 6 March 2024

Crystal structure of human PrimPol ternary complexCrystal structure of human PrimPol ternary complex

Structural highlights

5l2x is a 6 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:X-ray diffraction, Resolution 2.2Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PRIPO_HUMAN The disease is caused by mutations affecting the gene represented in this entry.

Function

PRIPO_HUMAN DNA primase and DNA polymerase able to initiate de novo DNA synthesis using dNTPs. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Involved in translesion synthesis via its primase activity by mediating uninterrupted fork progression after programmed or damage-induced fork arrest and by reinitiating DNA synthesis after dNTP depletion. Required for mitochondrial DNA (mtDNA) synthesis, suggesting it may be involved in DNA tolerance during the replication of mitochondrial DNA. Has non-overlapping function with POLH.[1] [2] [3] [4]

References

  1. ↑ Wan L, Lou J, Xia Y, Su B, Liu T, Cui J, Sun Y, Lou H, Huang J. hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the maintenance of genome integrity. EMBO Rep. 2013 Dec;14(12):1104-12. doi: 10.1038/embor.2013.159. Epub 2013 Oct 15. PMID:24126761 doi:http://dx.doi.org/10.1038/embor.2013.159
  2. ↑ Garcia-Gomez S, Reyes A, Martinez-Jimenez MI, Chocron ES, Mouron S, Terrados G, Powell C, Salido E, Mendez J, Holt IJ, Blanco L. PrimPol, an archaic primase/polymerase operating in human cells. Mol Cell. 2013 Nov 21;52(4):541-53. doi: 10.1016/j.molcel.2013.09.025. Epub 2013 , Oct 24. PMID:24207056 doi:http://dx.doi.org/10.1016/j.molcel.2013.09.025
  3. ↑ Mouron S, Rodriguez-Acebes S, Martinez-Jimenez MI, Garcia-Gomez S, Chocron S, Blanco L, Mendez J. Repriming of DNA synthesis at stalled replication forks by human PrimPol. Nat Struct Mol Biol. 2013 Dec;20(12):1383-9. doi: 10.1038/nsmb.2719. Epub 2013, Nov 17. PMID:24240614 doi:http://dx.doi.org/10.1038/nsmb.2719
  4. ↑ Bianchi J, Rudd SG, Jozwiakowski SK, Bailey LJ, Soura V, Taylor E, Stevanovic I, Green AJ, Stracker TH, Lindsay HD, Doherty AJ. PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA replication. Mol Cell. 2013 Nov 21;52(4):566-73. doi: 10.1016/j.molcel.2013.10.035. PMID:24267451 doi:http://dx.doi.org/10.1016/j.molcel.2013.10.035

5l2x, resolution 2.20Å

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OCA
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