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Folate deficiency regulates expression of DNA polymerase β in response to oxidative stress.
- Source :
-
Free radical biology & medicine [Free Radic Biol Med] 2011 Jan 15; Vol. 50 (2), pp. 270-80. Date of Electronic Publication: 2010 Nov 08. - Publication Year :
- 2011
-
Abstract
- Folate deficiency has been shown to influence carcinogenesis by creating an imbalance in the base excision repair (BER) pathway, affecting 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 of β-pol expression in response to oxidative stress is inhibited by folate deficiency at the level of gene expression. Alteration in the 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 or absence of folate. However, the promoter analysis studies show a differential binding of regulatory factors 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 factors 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 factors interacting with FARR, repressing the upregulation of the β-pol gene in response to oxidative stress.<br /> (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- 8-Hydroxy-2'-Deoxyguanosine
Animals
Base Sequence
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular pathology
Cell Nucleus genetics
Cells, Cultured
CpG Islands genetics
DNA Damage genetics
DNA Footprinting
DNA Repair genetics
Deoxyguanosine analogs & derivatives
Deoxyguanosine metabolism
Electrophoretic Mobility Shift Assay
Folic Acid metabolism
Liver cytology
Liver metabolism
Liver Neoplasms, Experimental genetics
Liver Neoplasms, Experimental pathology
Male
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Promoter Regions, Genetic genetics
DNA Methylation
DNA Polymerase beta genetics
Epigenomics
Folic Acid Deficiency genetics
Gene Expression Regulation
Oxidative Stress
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4596
- Volume :
- 50
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Free radical biology & medicine
- Publication Type :
- Academic Journal
- Accession number :
- 21070850
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2010.11.003