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Review
. 2018 Dec 14;10(12):513.
doi: 10.3390/cancers10120513.

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

Xiaowen Zhang  1 , Rong Li  2
Affiliations
Review

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

Xiaowen Zhang et al. Cancers (Basel). .

Abstract

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.

Keywords: BRCA1; chromatin organization; epigenetic regulation; transcriptional regulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The developmental hierarchy of human breast. (a) Cross-section of a normal breast duct. (b) Breast epithelial hierarchy and BRCA1-associated breast cancer.
Figure 2
Figure 2
Interactions between BRCA1 and transcription factors.
Figure 3
Figure 3
Model depicting BRCA1-dependent transcriptional regulation in tissue-specific tumor suppression. (a) BRCA1 is required for luminal differentiation. (b) BRCA1 prevents R-loop accumulation in the luminal lineage. (c) BRCA1 repairs double-strand breaks.
See this image and copyright information in PMC

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