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6gis

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Structural basis of human clamp sliding on DNA

Structural highlights

6gis is a 5 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 5l7c. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	5l7c
Gene:	PCNA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

Publication Abstract from PubMed

Sliding clamps encircle DNA and tether polymerases and other factors to the genomic template. However, the molecular mechanism of clamp sliding on DNA is unknown. Using crystallography, NMR and molecular dynamics simulations, here we show that the human clamp PCNA recognizes DNA through a double patch of basic residues within the ring channel, arranged in a right-hand spiral that matches the pitch of B-DNA. We propose that PCNA slides by tracking the DNA backbone via a 'cogwheel' mechanism based on short-lived polar interactions, which keep the orientation of the clamp invariant relative to DNA. Mutation of residues at the PCNA-DNA interface has been shown to impair the initiation of DNA synthesis by polymerase delta (pol delta). Therefore, our findings suggest that a clamp correctly oriented on DNA is necessary for the assembly of a replication-competent PCNA-pol delta holoenzyme.

Structural basis of human PCNA sliding on DNA.,De March M, Merino N, Barrera-Vilarmau S, Crehuet R, Onesti S, Blanco FJ, De Biasio A Nat Commun. 2017 Jan 10;8:13935. doi: 10.1038/ncomms13935. PMID:28071730^[3]

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

References

↑ Burkovics P, Hajdu I, Szukacsov V, Unk I, Haracska L. Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage. Nucleic Acids Res. 2009 Jul;37(13):4247-55. doi: 10.1093/nar/gkp357. Epub 2009, May 13. PMID:19443450 doi:10.1093/nar/gkp357
↑ Motegi A, Liaw HJ, Lee KY, Roest HP, Maas A, Wu X, Moinova H, Markowitz SD, Ding H, Hoeijmakers JH, Myung K. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12411-6. Epub 2008 Aug 21. PMID:18719106 doi:0805685105
↑ De March M, Merino N, Barrera-Vilarmau S, Crehuet R, Onesti S, Blanco FJ, De Biasio A. Structural basis of human PCNA sliding on DNA. Nat Commun. 2017 Jan 10;8:13935. doi: 10.1038/ncomms13935. PMID:28071730 doi:http://dx.doi.org/10.1038/ncomms13935

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6gis"

@@ Line 1: / Line 1: @@
 ==Structural basis of human clamp sliding on DNA==
-<StructureSection load='6gis' size='340' side='right' caption='[[6gis]], [[Resolution|resolution]] 2.82&Aring;' scene=''>
+<StructureSection load='6gis' size='340' side='right'caption='[[6gis]], [[Resolution|resolution]] 2.82&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6gis]] is a 5 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5l7c 5l7c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GIS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GIS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6gis]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5l7c 5l7c]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GIS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GIS FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5l7c|5l7c]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6gis FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gis OCA], [http://pdbe.org/6gis PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gis RCSB], [http://www.ebi.ac.uk/pdbsum/6gis PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gis ProSAT]</span></td></tr>
 </table>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 6gis" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Proliferating Cell Nuclear Antigen|Proliferating Cell Nuclear Antigen]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Barrera-Vilarmau, S]]
 [[Category: Biasio, A De]]

6gis

From Proteopedia

Current revision

Structural basis of human clamp sliding on DNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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