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4gk5

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Revision as of 01:12, 5 August 2016

Crystal structure of human Rev3-Rev7-Rev1-Polkappa complex

Structural highlights

4gk5 is a 7 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4gk0
Gene:	MAD2L2, MAD2B, REV7 (HUMAN), REV3L, POLZ, REV3 (HUMAN), REV1, REV1L (HUMAN)
Activity:	DNA-directed DNA polymerase, with EC number 2.7.7.7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[POLK_HUMAN] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] [MD2L2_HUMAN] Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.^[8] ^[9] ^[10] ^[11] ^[12] [REV1_HUMAN] Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.^[13] ^[14] ^[15] ^[16] ^[17] [DPOLZ_HUMAN] Interacts with MAD2L2 to form the error prone DNA polymerase zeta involved in translesion DNA synthesis.

Publication Abstract from PubMed

In addition to DNA repair pathways, cells utilize translesion DNA synthesis (TLS) to bypass DNA lesions during replication. During TLS, Y-family DNA polymerase (Poleta, Polkappa, Poli and Rev1) inserts specific nucleotide opposite preferred DNA lesions, and then Polzeta consisting of two subunits, Rev3 and Rev7, carries out primer extension. Here, we report the complex structures of Rev3-Rev7-Rev1(CTD) and Rev3-Rev7-Rev1(CTD)-Polkappa(RIR). These two structures demonstrate that Rev1(CTD) contains separate binding sites for Polkappa and Rev7. Our BIAcore experiments provide additional support for the notion that the interaction between Rev3 and Rev7 increases the affinity of Rev7 and Rev1. We also verified through FRET experiment that Rev1, Rev3, Rev7 and Polkappa form a stable quaternary complex in vivo, thereby suggesting an efficient switching mechanism where the "inserter" polymerase can be immediately replaced by an "extender" polymerase within the same quaternary complex.

Structural insights into the assembly of human translesion polymerase complexes.,Xie W, Yang X, Xu M, Jiang T Protein Cell. 2012 Nov;3(11):864-74. doi: 10.1007/s13238-012-2102-x. Epub 2012, Nov 10. PMID:23143872^[18]

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

References

↑ Ogi T, Kato T Jr, Kato T, Ohmori H. Mutation enhancement by DINB1, a mammalian homologue of the Escherichia coli mutagenesis protein dinB. Genes Cells. 1999 Nov;4(11):607-18. PMID:10620008
↑ Gerlach VL, Feaver WJ, Fischhaber PL, Friedberg EC. Purification and characterization of pol kappa, a DNA polymerase encoded by the human DINB1 gene. J Biol Chem. 2001 Jan 5;276(1):92-8. PMID:11024016 doi:http://dx.doi.org/10.1074/jbc.M004413200
↑ Fischhaber PL, Gerlach VL, Feaver WJ, Hatahet Z, Wallace SS, Friedberg EC. Human DNA polymerase kappa bypasses and extends beyond thymine glycols during translesion synthesis in vitro, preferentially incorporating correct nucleotides. J Biol Chem. 2002 Oct 4;277(40):37604-11. Epub 2002 Jul 26. PMID:12145297 doi:10.1074/jbc.M206027200
↑ Haracska L, Prakash L, Prakash S. Role of human DNA polymerase kappa as an extender in translesion synthesis. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16000-5. Epub 2002 Nov 20. PMID:12444249 doi:10.1073/pnas.252524999
↑ Wolfle WT, Washington MT, Prakash L, Prakash S. Human DNA polymerase kappa uses template-primer misalignment as a novel means for extending mispaired termini and for generating single-base deletions. Genes Dev. 2003 Sep 1;17(17):2191-9. PMID:12952891 doi:http://dx.doi.org/10.1101/gad.1108603
↑ Haracska L, Prakash L, Prakash S. A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair. Genes Dev. 2003 Nov 15;17(22):2777-85. PMID:14630940 doi:10.1101/gad.1146103
↑ Yasui M, Suzuki N, Miller H, Matsuda T, Matsui S, Shibutani S. Translesion synthesis past 2'-deoxyxanthosine, a nitric oxide-derived DNA adduct, by mammalian DNA polymerases. J Mol Biol. 2004 Nov 26;344(3):665-74. PMID:15533436 doi:S0022-2836(04)01222-7
↑ Pfleger CM, Salic A, Lee E, Kirschner MW. Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1. Genes Dev. 2001 Jul 15;15(14):1759-64. PMID:11459825 doi:10.1101/gad.897901
↑ Chen J, Fang G. MAD2B is an inhibitor of the anaphase-promoting complex. Genes Dev. 2001 Jul 15;15(14):1765-70. PMID:11459826 doi:10.1101/gad.898701
↑ Iwai H, Kim M, Yoshikawa Y, Ashida H, Ogawa M, Fujita Y, Muller D, Kirikae T, Jackson PK, Kotani S, Sasakawa C. A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host cell cycling. Cell. 2007 Aug 24;130(4):611-23. PMID:17719540 doi:10.1016/j.cell.2007.06.043
↑ Zhang L, Yang SH, Sharrocks AD. Rev7/MAD2B links c-Jun N-terminal protein kinase pathway signaling to activation of the transcription factor Elk-1. Mol Cell Biol. 2007 Apr;27(8):2861-9. Epub 2007 Feb 12. PMID:17296730 doi:10.1128/MCB.02276-06
↑ Hong CF, Chou YT, Lin YS, Wu CW. MAD2B, a novel TCF4-binding protein, modulates TCF4-mediated epithelial-mesenchymal transdifferentiation. J Biol Chem. 2009 Jul 17;284(29):19613-22. doi: 10.1074/jbc.M109.005017. Epub, 2009 May 14. PMID:19443654 doi:10.1074/jbc.M109.005017
↑ Lin W, Xin H, Zhang Y, Wu X, Yuan F, Wang Z. The human REV1 gene codes for a DNA template-dependent dCMP transferase. Nucleic Acids Res. 1999 Nov 15;27(22):4468-75. PMID:10536157
↑ Gibbs PE, Wang XD, Li Z, McManus TP, McGregor WG, Lawrence CW, Maher VM. The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by UV light. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4186-91. PMID:10760286
↑ Masuda Y, Takahashi M, Tsunekuni N, Minami T, Sumii M, Miyagawa K, Kamiya K. Deoxycytidyl transferase activity of the human REV1 protein is closely associated with the conserved polymerase domain. J Biol Chem. 2001 May 4;276(18):15051-8. Epub 2001 Jan 22. PMID:11278384 doi:10.1074/jbc.M008082200
↑ Murakumo Y, Ogura Y, Ishii H, Numata S, Ichihara M, Croce CM, Fishel R, Takahashi M. Interactions in the error-prone postreplication repair proteins hREV1, hREV3, and hREV7. J Biol Chem. 2001 Sep 21;276(38):35644-51. Epub 2001 Aug 2. PMID:11485998 doi:10.1074/jbc.M102051200
↑ Kim H, Yang K, Dejsuphong D, D'Andrea AD. Regulation of Rev1 by the Fanconi anemia core complex. Nat Struct Mol Biol. 2012 Jan 22;19(2):164-70. doi: 10.1038/nsmb.2222. PMID:22266823 doi:10.1038/nsmb.2222
↑ Xie W, Yang X, Xu M, Jiang T. Structural insights into the assembly of human translesion polymerase complexes. Protein Cell. 2012 Nov;3(11):864-74. doi: 10.1007/s13238-012-2102-x. Epub 2012, Nov 10. PMID:23143872 doi:http://dx.doi.org/10.1007/s13238-012-2102-x

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/4gk5"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human Rev3-Rev7-Rev1-Polkappa complex==
 <StructureSection load='4gk5' size='340' side='right' caption='[[4gk5]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4gk5]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Clostridium_acetobutylicum Clostridium acetobutylicum] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GK5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GK5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4gk5]] is a 7 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=4GK5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GK5 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gk0|4gk0]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAD2L2, MAD2B, REV7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), REV3L, POLZ, REV3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1488 Clostridium acetobutylicum]), REV1, REV1L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAD2L2, MAD2B, REV7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), REV3L, POLZ, REV3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), REV1, REV1L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></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=4gk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gk5 RCSB], [http://www.ebi.ac.uk/pdbsum/4gk5 PDBsum]</span></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=4gk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk5 OCA], [http://pdbe.org/4gk5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gk5 RCSB], [http://www.ebi.ac.uk/pdbsum/4gk5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gk5 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4gk5" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Clostridium acetobutylicum]]
 [[Category: DNA-directed DNA polymerase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Min, X]]
 [[Category: Tao, J]]

4gk5

From Proteopedia

Revision as of 01:12, 5 August 2016

Crystal structure of human Rev3-Rev7-Rev1-Polkappa complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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