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BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression

Germ-line mutations in breast cancer susceptibility gene 1 (BRCA1) predominantly predispose women to breast and ovarian cancers. BRCA1 is best known for its functions in maintenance of genomic integrity including repairing DNA double-strand breaks through homologous recombination and suppressing DNA...

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Detalles Bibliográficos
Autores principales: Zhang, Xiaowen, Li, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316118/
https://www.ncbi.nlm.nih.gov/pubmed/30558184
http://dx.doi.org/10.3390/cancers10120513
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author Zhang, Xiaowen
Li, Rong
author_facet Zhang, Xiaowen
Li, Rong
author_sort Zhang, Xiaowen
collection PubMed
description Germ-line mutations in breast cancer susceptibility gene 1 (BRCA1) predominantly predispose women to breast and ovarian cancers. BRCA1 is best known for its functions in maintenance of genomic integrity including repairing DNA double-strand breaks through homologous recombination and suppressing DNA replication stress. However, whether these universally important BRCA1 functions in maintenance of genomic stability are sufficient to account for its tissue-specific tumor-suppressing function remains unclear. Accumulating evidence indicates that there are previously underappreciated roles of BRCA1 in transcriptional regulation and chromatin remodeling. In this review, we discuss the functional significance of interactions between BRCA1 and various transcription factors, its role in epigenetic regulation and chromatin dynamics, and BRCA1-dependent crosstalk between the machineries of transcription and genome integrity. Furthermore, we propose a model of how transcriptional regulation could contribute to tissue-dependent tumor-suppressing function of BRCA1.
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spelling pubmed-63161182019-01-09 BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression Zhang, Xiaowen Li, Rong Cancers (Basel) Review Germ-line mutations in breast cancer susceptibility gene 1 (BRCA1) predominantly predispose women to breast and ovarian cancers. BRCA1 is best known for its functions in maintenance of genomic integrity including repairing DNA double-strand breaks through homologous recombination and suppressing DNA replication stress. However, whether these universally important BRCA1 functions in maintenance of genomic stability are sufficient to account for its tissue-specific tumor-suppressing function remains unclear. Accumulating evidence indicates that there are previously underappreciated roles of BRCA1 in transcriptional regulation and chromatin remodeling. In this review, we discuss the functional significance of interactions between BRCA1 and various transcription factors, its role in epigenetic regulation and chromatin dynamics, and BRCA1-dependent crosstalk between the machineries of transcription and genome integrity. Furthermore, we propose a model of how transcriptional regulation could contribute to tissue-dependent tumor-suppressing function of BRCA1. MDPI 2018-12-14 /pmc/articles/PMC6316118/ /pubmed/30558184 http://dx.doi.org/10.3390/cancers10120513 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zhang, Xiaowen
Li, Rong
BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression
title BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression
title_full BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression
title_fullStr BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression
title_full_unstemmed BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression
title_short BRCA1-Dependent Transcriptional Regulation: Implication in Tissue-Specific Tumor Suppression
title_sort brca1-dependent transcriptional regulation: implication in tissue-specific tumor suppression
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316118/
https://www.ncbi.nlm.nih.gov/pubmed/30558184
http://dx.doi.org/10.3390/cancers10120513
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