Folate deficiency regulates expression of DNA polymerase β in response to oxidative stress
| Autor: | Ahmad R. Heydari, Erin V. Papakonstantinou, Hiral V. Patel, Tom Prychitko, Mahbuba E. Chowdhury, Diane C. Cabelof, Archana Unnikrishnan, Lisa F. Ventrella-Lucente, Amanda B. Pilling |
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| Rok vydání: | 2010 |
| Předmět: |
Epigenomics
Male Carcinoma Hepatocellular DNA Repair DNA repair DNA damage Molecular Sequence Data DNA Footprinting Electrophoretic Mobility Shift Assay Biology Folic Acid Deficiency medicine.disease_cause Biochemistry Article Mice Folic Acid Liver Neoplasms Experimental Physiology (medical) Gene expression medicine Animals Promoter Regions Genetic Cells Cultured DNA Polymerase beta Regulation of gene expression Cell Nucleus Base Sequence Deoxyguanosine Promoter Base excision repair DNA Methylation Molecular biology Mice Inbred C57BL Oxidative Stress Gene Expression Regulation Liver 8-Hydroxy-2'-Deoxyguanosine DNA methylation CpG Islands Carcinogenesis DNA Damage |
| Zdroj: | Free radical biologymedicine. 50(2) |
| ISSN: | 1873-4596 |
| Popis: | Folate deficiency has been shown to influence carcinogenesis by creating an imbalance in the base excision repair (BER) pathway impacting BER homeostasis. The inability to mount a BER response to oxidative stress in a folate deficient environment results in the accumulation of DNA repair intermediates, i.e., DNA strand breaks. Our data indicate that upregulation in β-pol expression in response to oxidative stress is inhibited by folate deficiency at the level of gene expression. Alteration in expression of β-pol in a folate deficient environment is not due to epigenetic changes in the core promoter of the β-pol gene, i.e., the CpG islands within the β-pol promoter remain unmethylated in the presence and/or absence of folate. However, the promoter analysis studies show a differential binding of regulatory factor(s) to the −36 to −7 region (the folic acid response region, FARR) within the core promoter of β-pol. Moreover, we observe a tight correlation between the level of binding of regulatory factor(s) with the FARR and inhibition of β-pol expression. Based on these findings, we propose that folate deficiency results in an upregulation/stability of negative regulatory factor(s) interacting with FARR, repressing the upregulation of the β-pol gene in response to oxidative stress. |
| Databáze: | OpenAIRE |
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