5n8a

From Proteopedia

(Difference between revisions)

Current revision

Structure of RPA70N in complex with PrimPol (fragment 480-560)

Structural highlights

5n8a is a 2 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 1.28Å
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]

Publication Abstract from PubMed

DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multifunctional replicative enzyme called primase-polymerase (PrimPol) that is capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impediments. Here, we report that PrimPol is recruited to reprime through its interaction with RPA. Using biophysical and crystallographic approaches, we identify that PrimPol possesses two RPA-binding motifs and ascertained the key residues required for these interactions. We demonstrate that one of these motifs is critical for PrimPol's recruitment to stalled replication forks in vivo. In addition, biochemical analysis reveals that RPA serves to stimulate the primase activity of PrimPol. Together, these findings provide significant molecular insights into PrimPol's mode of recruitment to stalled forks to facilitate repriming and restart.

Molecular basis for PrimPol recruitment to replication forks by RPA.,Guilliam TA, Brissett NC, Ehlinger A, Keen BA, Kolesar P, Taylor EM, Bailey LJ, Lindsay HD, Chazin WJ, Doherty AJ Nat Commun. 2017 May 23;8:15222. doi: 10.1038/ncomms15222. PMID:28534480^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ Guilliam TA, Brissett NC, Ehlinger A, Keen BA, Kolesar P, Taylor EM, Bailey LJ, Lindsay HD, Chazin WJ, Doherty AJ. Molecular basis for PrimPol recruitment to replication forks by RPA. Nat Commun. 2017 May 23;8:15222. doi: 10.1038/ncomms15222. PMID:28534480 doi:http://dx.doi.org/10.1038/ncomms15222

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5n8a"

Categories: Homo sapiens | Large Structures | Brissett NC | Doherty AJ

@@ Line 3: / Line 3: @@
 <StructureSection load='5n8a' size='340' side='right'caption='[[5n8a]], [[Resolution|resolution]] 1.28&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5n8a]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N8A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5N8A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5n8a]] is a 2 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=5N8A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N8A FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5n85|5n85]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.28&#8491;</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=5n8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n8a OCA], [http://pdbe.org/5n8a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n8a RCSB], [http://www.ebi.ac.uk/pdbsum/5n8a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n8a ProSAT]</span></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=5n8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n8a OCA], [https://pdbe.org/5n8a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n8a RCSB], [https://www.ebi.ac.uk/pdbsum/5n8a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n8a ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/PRIPO_HUMAN PRIPO_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/PRIPO_HUMAN PRIPO_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://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>  [[http://www.uniprot.org/uniprot/RFA1_HUMAN RFA1_HUMAN]] Plays an essential role in several cellular processes in DNA metabolism including replication, recombination and DNA repair. Binds and subsequently stabilizes single-stranded DNA intermediates and thus prevents complementary DNA from reannealing.<ref>PMID:19116208</ref> <ref>PMID:19996105</ref>   Functions as component of the alternative replication protein A complex (aRPA). aRPA binds single-stranded DNA and probably plays a role in DNA repair; it does not support chromosomal DNA replication and cell cycle progression through S-phase. In vitro, aRPA cannot promote efficient priming by DNA polymerase alpha but supports DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange.<ref>PMID:19116208</ref> <ref>PMID:19996105</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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Brissett, N C]]
+[[Category: Brissett NC]]
-[[Category: Doherty, A J]]
+[[Category: Doherty AJ]]
-[[Category: Basic cleft]]
-[[Category: Complex]]
-[[Category: Protein binding]]
-[[Category: Replication]]

5n8a

From Proteopedia

Current revision

Structure of RPA70N in complex with PrimPol (fragment 480-560)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox