This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5l7c

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 01:19, 16 November 2017

Structural basis of human clamp sliding on DNA

Structural highlights

5l7c is a 5 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5l7c"

@@ Line 3: / Line 3: @@
 <StructureSection load='5l7c' size='340' side='right' caption='[[5l7c]], [[Resolution|resolution]] 2.82&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5l7c]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L7C FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5l7c]] is a 5 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=5L7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5L7C FirstGlance]. <br>
-</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=5l7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l7c OCA], [http://pdbe.org/5l7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l7c RCSB], [http://www.ebi.ac.uk/pdbsum/5l7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l7c ProSAT]</span></td></tr>
+</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=5l7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l7c OCA], [http://pdbe.org/5l7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l7c RCSB], [http://www.ebi.ac.uk/pdbsum/5l7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l7c ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Barrera-Vilarmau, S]]
 [[Category: Biasio, A De]]

5l7c

From Proteopedia

Revision as of 01:19, 16 November 2017

Structural basis of human clamp sliding on DNA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox