| Structural highlights
Function
[POLH_YEAST] 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. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. Efficiently incorporates nucleotides opposite to other UV or oxidative DNA damages like O(6)-methylguanine, 7,8-dihydro-8-oxoguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine of 2'-deoxyguanosine (FaPydG), or p-benzoquinone DNA adducts.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34]
Publication Abstract from PubMed
Eukaryotic DNA polymerase eta catalyzes translesion synthesis of thymine dimers and 8-oxoguanines. It is comprised of a polymerase domain and a C-terminal region, both of which are required for its biological function. The C-terminal region mediates interactions with proliferating cell nuclear antigen (PCNA) and other translesion synthesis proteins such as Rev1. This region contains a ubiquitin-binding/zinc-binding (UBZ) motif and a PCNA-interacting protein (PIP) motif. Currently little structural information is available for this region of polymerase eta. Using a combination of approaches-including genetic complementation assays, X-ray crystallography, Langevin dynamics simulations, and small-angle X-ray scattering-we show that the C-terminal region is partially unstructured and has high conformational flexibility. This implies that the C-terminal region acts as a flexible tether linking the polymerase domain to PCNA thereby increasing its local concentration. Such tethering would facilitate the sampling of translesion synthesis polymerases to ensure that the most appropriate one is selected to bypass the lesion.
The C-terminal region of translesion synthesis DNA polymerase eta is partially unstructured and has high conformational flexibility.,Powers KT, Elcock AH, Washington MT Nucleic Acids Res. 2018 Jan 29. pii: 4827929. doi: 10.1093/nar/gky031. PMID:29385534[35]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Washington MT, Johnson RE, Prakash S, Prakash L. Accuracy of thymine-thymine dimer bypass by Saccharomyces cerevisiae DNA polymerase eta. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3094-9. PMID:10725365 doi:http://dx.doi.org/10.1073/pnas.050491997
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- ↑ Washington MT, Wolfle WT, Spratt TE, Prakash L, Prakash S. Yeast DNA polymerase eta makes functional contacts with the DNA minor groove only at the incoming nucleoside triphosphate. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5113-8. Epub 2003 Apr 11. PMID:12692307 doi:http://dx.doi.org/10.1073/pnas.0837578100
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- ↑ Hwang H, Taylor JS. Evidence for Watson-Crick and not Hoogsteen or wobble base pairing in the selection of nucleotides for insertion opposite pyrimidines and a thymine dimer by yeast DNA pol eta. Biochemistry. 2005 Mar 29;44(12):4850-60. PMID:15779911 doi:http://dx.doi.org/10.1021/bi048244+
- ↑ Xie Z, Zhang Y, Guliaev AB, Shen H, Hang B, Singer B, Wang Z. The p-benzoquinone DNA adducts derived from benzene are highly mutagenic. DNA Repair (Amst). 2005 Dec 8;4(12):1399-409. Epub 2005 Sep 21. PMID:16181813 doi:http://dx.doi.org/S1568-7864(05)00215-6
- ↑ Gibbs PE, McDonald J, Woodgate R, Lawrence CW. The relative roles in vivo of Saccharomyces cerevisiae Pol eta, Pol zeta, Rev1 protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutane dimer. Genetics. 2005 Feb;169(2):575-82. Epub 2004 Nov 1. PMID:15520252 doi:http://dx.doi.org/genetics.104.034611
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- ↑ Vu B, Cannistraro VJ, Sun L, Taylor JS. DNA synthesis past a 5-methylC-containing cis-syn-cyclobutane pyrimidine dimer by yeast pol eta is highly nonmutagenic. Biochemistry. 2006 Aug 1;45(30):9327-35. PMID:16866379 doi:http://dx.doi.org/10.1021/bi0602009
- ↑ Abdulovic AL, Jinks-Robertson S. The in vivo characterization of translesion synthesis across UV-induced lesions in Saccharomyces cerevisiae: insights into Pol zeta- and Pol eta-dependent frameshift mutagenesis. Genetics. 2006 Mar;172(3):1487-98. Epub 2005 Dec 30. PMID:16387871 doi:http://dx.doi.org/genetics.105.052480
- ↑ Zhao B, Wang J, Geacintov NE, Wang Z. Poleta, Polzeta and Rev1 together are required for G to T transversion mutations induced by the (+)- and (-)-trans-anti-BPDE-N2-dG DNA adducts in yeast cells. Nucleic Acids Res. 2006 Jan 13;34(2):417-25. Print 2006. PMID:16415180 doi:http://dx.doi.org/34/2/417
- ↑ Powers KT, Elcock AH, Washington MT. The C-terminal region of translesion synthesis DNA polymerase eta is partially unstructured and has high conformational flexibility. Nucleic Acids Res. 2018 Jan 29. pii: 4827929. doi: 10.1093/nar/gky031. PMID:29385534 doi:http://dx.doi.org/10.1093/nar/gky031
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