| Structural highlights
3pzp is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | DTP, MG |
| NonStd Res: | TTD |
| Related: | 1t94, 2oh2, 3in5 |
| Gene: | POLK, DINB1 (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]
Publication Abstract from PubMed
Exposure of DNA to UV radiation causes covalent linkages between adjacent pyrimidines. The most common lesion found in DNA from these UV-induced linkages is the cis-syn cyclobutane pyrimidine dimer. Human DNA polymerase kappa (Polkappa), a member of the Y-family of DNA polymerases, is unable to insert nucleotides opposite the 3'T of a cis-syn T-T dimer, but it can efficiently extend from a nucleotide inserted opposite the 3'T of the dimer by another DNA polymerase. We present here the structure of human Polkappa in the act of inserting a nucleotide opposite the 5'T of the cis-syn T-T dimer. The structure reveals a constrained active-site cleft that is unable to accommodate the 3'T of a cis-syn T-T dimer but is remarkably well adapted to accommodate the 5'T via Watson-Crick base pairing, in accord with a proposed role for Polkappa in the extension reaction opposite from cyclobutane pyrimidine dimers in vivo.
Role of human DNA polymerase kappa in extension opposite from a cis-syn thymine dimer.,Vasquez-Del Carpio R, Silverstein TD, Lone S, Johnson RE, Prakash L, Prakash S, Aggarwal AK J Mol Biol. 2011 Apr 29;408(2):252-61. Epub 2011 Feb 24. PMID:21354175[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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:https://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:https://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
- ↑ Vasquez-Del Carpio R, Silverstein TD, Lone S, Johnson RE, Prakash L, Prakash S, Aggarwal AK. Role of human DNA polymerase kappa in extension opposite from a cis-syn thymine dimer. J Mol Biol. 2011 Apr 29;408(2):252-61. Epub 2011 Feb 24. PMID:21354175 doi:10.1016/j.jmb.2011.02.042
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