Journal article
Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase beta and a de novo DNA Methyltransferase
Cells (Basel, Switzerland), v 9(1)
01 Jan 2020
PMID: 31963223
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
DNA damage and base excision repair (BER) are actively involved in the modulation of DNA methylation and demethylation. However, the underlying molecular mechanisms remain unclear. In this study, we seek to understand the mechanisms by exploring the effects of oxidative DNA damage on the DNA methylation pattern of the tumor suppressor breast cancer 1 (BRCA1) gene in the human embryonic kidney (HEK) HEK293H cells. We found that oxidative DNA damage simultaneously induced DNA demethylation and generation of new methylation sites at the CpGs located at the promoter and transcribed regions of the gene ranging from -189 to +27 in human cells. We demonstrated that DNA damage-induced demethylation was mediated by nucleotide misincorporation by DNA polymerase beta (pol beta). Surprisingly, we found that the generation of new DNA methylation sites was mediated by coordination between pol beta and the de novo DNA methyltransferase, DNA methyltransferase 3b (DNMT3b), through the interaction between the two enzymes in the promoter and encoding regions of the BRCA1 gene. Our study provides the first evidence that oxidative DNA damage can cause dynamic changes in DNA methylation in the BRCA1 gene through the crosstalk between BER and de novo DNA methylation.
Metrics
Details
- Title
- Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase beta and a de novo DNA Methyltransferase
- Creators
- Zhongliang Jiang - Florida International UniversityYanhao Lai - Florida International UniversityJill M. Beaver - Florida International UniversityPawlos S. Tsegay - Florida International UniversityMing-Lang Zhao - Triangle : Action, Discours, Pensée politique et économiqueJulie K. Horton - National Institute of Environmental Health SciencesMarco Zamora - Florida International UniversityHayley L. Rein - Florida International UniversityFrank Miralles - Florida International UniversityMohammad Shaver - Florida International UniversityJoshua D. Hutcheson - Florida International UniversityIrina Agoulnik - Florida International UniversitySamuel H. Wilson - National Institute of Environmental Health SciencesYuan Liu - Florida International University
- Publication Details
- Cells (Basel, Switzerland), v 9(1)
- Publisher
- Mdpi
- Number of pages
- 20
- Grant note
- R01ES023569 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Z01 ES050159 / Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000515398200225
- Scopus ID
- 2-s2.0-85086918870
- Other Identifier
- 991020100086404721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology