Interferon Regulatory Factor 1 Transactivates Expression of Human DNA Polymerase η in Response to Carcinogen N-methyl-N'-nitro-N-nitrosoguanidine

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Feb 28

PMID 22367195

Citations 13

Authors

Hongyan Qi

Huifang Zhu

Meng Lou

Yanfeng Fan

Hong Liu

Jing Shen

Zhongjie Li

Xue Lv

Jianzhen Shan

Lijun Zhu

Y Eugene Chin

Jimin Shao

Affiliations

Soon will be listed here.

Abstract

DNA polymerase η (Polη) implements translesion DNA synthesis but has low fidelity in replication. We have previously shown that Polη plays an important role in the genesis of nontargeted mutations at undamaged DNA sites in cells exposed to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Here, we report that MNNG-induced Polη expression in an interferon regulatory factor 1 (IRF1)-dependent manner in human cells. Mutagenesis analysis showed that four critical residues (Arg-82, Cys-83, Asn-86, and Ser-87) located in the IRF family conserved DNA binding domain-helix α3 were involved in DNA binding and POLH transactivation by IRF1. Furthermore, Polη up-regulation induced by IRF1 was responsible for the increase of mutation frequency in a SupF shuttle plasmid replicated in the MNNG-exposed cells. Interestingly, IRF1 was acetylated by the histone acetyltransferase CBP in these cells. Lys → Arg substitution revealed that Lys-78 of helix α3 was the major acetylation site, and the IRF1-K78R mutation partially inhibited DNA binding and its transcriptional activity. Thus, we propose that IRF1 activation is responsible for MNNG-induced Polη up-regulation, which contributes to mutagenesis and ultimately carcinogenesis in cells.

Citing Articles

Integrated Analysis of Transcriptome Profiles and lncRNA-miRNA-mRNA Competing Endogenous RNA Regulatory Network to Identify Biological Functional Effects of Genes and Pathways Associated with Johne's Disease in Dairy Cattle.

Ghafouri F, Dehghanian Reyhan V, Sadeghi M, Miraei-Ashtiani S, Kastelic J, Barkema H Noncoding RNA. 2024; 10(4).

PMID: 39051372 PMC: 11270299. DOI: 10.3390/ncrna10040038.

Beyond the Lesion: Back to High Fidelity DNA Synthesis.

Kaszubowski J, Trakselis M Front Mol Biosci. 2022; 8:811540.

PMID: 35071328 PMC: 8766770. DOI: 10.3389/fmolb.2021.811540.

Exosomal lncRNA SCIRT/miR-665 Transferring Promotes Lung Cancer Cell Metastasis through the Inhibition of HEYL.

Wang Z, Lin M, He L, Qi H, Shen J, Ying K J Oncol. 2021; 2021:9813773.

PMID: 34349799 PMC: 8328715. DOI: 10.1155/2021/9813773.

IκB kinase-ε-mediated phosphorylation triggers IRF-1 degradation in breast cancer cells.

Remoli A, Sgarbanti M, Perrotti E, Acchioni M, Orsatti R, Acchioni C Neoplasia. 2020; 22(10):459-469.

PMID: 32784074 PMC: 7419274. DOI: 10.1016/j.neo.2020.07.004.

Regulation of the abundance of Y-family polymerases in the cell cycle of budding yeast in response to DNA damage.

Sobolewska A, Halas A, Plachta M, McIntyre J, Sledziewska-Gojska E Curr Genet. 2020; 66(4):749-763.

PMID: 32076806 PMC: 7363672. DOI: 10.1007/s00294-020-01061-3.

References

Livneh Z . Keeping mammalian mutation load in check: regulation of the activity of error-prone DNA polymerases by p53 and p21. Cell Cycle. 2006; 5(17):1918-22. DOI: 10.4161/cc.5.17.3193. View

Johnson R, Prakash S, Prakash L . Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta. Science. 1999; 283(5404):1001-4. DOI: 10.1126/science.283.5404.1001. View

Zhu H, Fan Y, Jiang H, Shen J, Qi H, Mei R . Response of human DNA polymerase ι promoter to N-methyl-N'-nitro-N-nitrosoguanidine. Environ Toxicol Pharmacol. 2011; 29(1):79-86. DOI: 10.1016/j.etap.2009.11.001. View

McCulloch S, Kunkel T . The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell Res. 2008; 18(1):148-61. PMC: 3639319. DOI: 10.1038/cr.2008.4. View

Ohmori Y, Schreiber R, Hamilton T . Synergy between interferon-gamma and tumor necrosis factor-alpha in transcriptional activation is mediated by cooperation between signal transducer and activator of transcription 1 and nuclear factor kappaB. J Biol Chem. 1997; 272(23):14899-907. DOI: 10.1074/jbc.272.23.14899. View

Kim S, Michael W . Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. elegans. Mol Cell. 2008; 32(6):757-66. PMC: 2646262. DOI: 10.1016/j.molcel.2008.11.016. View

Liu G, Shang Y, Yu Y . Induced endoplasmic reticulum (ER) stress and binding of over-expressed ER specific chaperone GRP78/BiP with dimerized epidermal growth factor receptor in mammalian cells exposed to low concentration of N-methyl-N'-nitro-N-nitrosoguanidine. Mutat Res. 2006; 596(1-2):12-21. DOI: 10.1016/j.mrfmmm.2005.10.015. View

Percario Z, Giandomenico V, Fiorucci G, Chiantore M, Vannucchi S, Hiscott J . Retinoic acid is able to induce interferon regulatory factor 1 in squamous carcinoma cells via a STAT-1 independent signalling pathway. Cell Growth Differ. 1999; 10(4):263-70. View

Zhang Y, Yuan F, Wu X, Rechkoblit O, Taylor J, Geacintov N . Error-prone lesion bypass by human DNA polymerase eta. Nucleic Acids Res. 2000; 28(23):4717-24. PMC: 115171. DOI: 10.1093/nar/28.23.4717. View

10.

Li K, Wang R, Lozada E, Fan W, Orren D, Luo J . Acetylation of WRN protein regulates its stability by inhibiting ubiquitination. PLoS One. 2010; 5(4):e10341. PMC: 2859066. DOI: 10.1371/journal.pone.0010341. View

11.

Smith H, Nathans D . Letter: A suggested nomenclature for bacterial host modification and restriction systems and their enzymes. J Mol Biol. 1973; 81(3):419-23. DOI: 10.1016/0022-2836(73)90152-6. View

12.

Haracska L, Johnson R, Unk I, Phillips B, Hurwitz J, Prakash L . Physical and functional interactions of human DNA polymerase eta with PCNA. Mol Cell Biol. 2001; 21(21):7199-206. PMC: 99895. DOI: 10.1128/MCB.21.21.7199-7206.2001. View

13.

Caron C, Boyault C, Khochbin S . Regulatory cross-talk between lysine acetylation and ubiquitination: role in the control of protein stability. Bioessays. 2005; 27(4):408-15. DOI: 10.1002/bies.20210. View

14.

Kawamoto T, Araki K, Sonoda E, Yamashita Y, Harada K, Kikuchi K . Dual roles for DNA polymerase eta in homologous DNA recombination and translesion DNA synthesis. Mol Cell. 2005; 20(5):793-9. DOI: 10.1016/j.molcel.2005.10.016. View

15.

Yamashita S, Nomoto T, Abe M, Tatematsu M, Sugimura T, Ushijima T . Persistence of gene expression changes in stomach mucosae induced by short-term N-methyl-N'-nitro-N-nitrosoguanidine treatment and their presence in stomach cancers. Mutat Res. 2004; 549(1-2):185-93. DOI: 10.1016/j.mrfmmm.2003.10.009. View

16.

Suhara W, Yoneyama M, Kitabayashi I, Fujita T . Direct involvement of CREB-binding protein/p300 in sequence-specific DNA binding of virus-activated interferon regulatory factor-3 holocomplex. J Biol Chem. 2002; 277(25):22304-13. DOI: 10.1074/jbc.M200192200. View

17.

Luo Y, Yang J, Yu Y . [Establishment of a cell line with antisense-blocked POLH and the role of POLH in alkylating agent MNNG induced nontargeted mutagenesis]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2003; 32(5):398-402. DOI: 10.3785/j.issn.1008-9292.2003.05.007. View

18.

Acharya N, Yoon J, Gali H, Unk I, Haracska L, Johnson R . Roles of PCNA-binding and ubiquitin-binding domains in human DNA polymerase eta in translesion DNA synthesis. Proc Natl Acad Sci U S A. 2008; 105(46):17724-9. PMC: 2584706. DOI: 10.1073/pnas.0809844105. View

19.

Shen J, Wu M, Yu Y . Proteomic profiling for cellular responses to different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine. J Proteome Res. 2006; 5(2):385-95. DOI: 10.1021/pr0502875. View

20.

Kim S, Kang H, Na H, Lee M . Trichostatin A enhances acetylation as well as protein stability of ERalpha through induction of p300 protein. Breast Cancer Res. 2010; 12(2):R22. PMC: 2879569. DOI: 10.1186/bcr2562. View