Strong preference of BRCA1 protein to topologically constrained non-B DNA structures

Brazda, Vaclav, Haronikova, Lucia, Liao, Jack C. C., Fridrichova, Helena and Jagelska, Eva B. (2016) Strong preference of BRCA1 protein to topologically constrained non-B DNA structures. BMC Molecular Biology, 17 14: 1-9. doi:10.1186/s12867-016-0068-6

Author Brazda, Vaclav
Haronikova, Lucia
Liao, Jack C. C.
Fridrichova, Helena
Jagelska, Eva B.
Title Strong preference of BRCA1 protein to topologically constrained non-B DNA structures
Journal name BMC Molecular Biology   Check publisher's open access policy
ISSN 1471-2199
Publication date 2016-06
Year available 2016
Sub-type Article (original research)
DOI 10.1186/s12867-016-0068-6
Open Access Status DOI
Volume 17
Issue 14
Start page 1
End page 9
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central
Collection year 2017
Language eng
Formatted abstract
The breast and ovarian cancer susceptibility gene BRCA1 encodes a multifunctional tumor suppressor protein BRCA1, which is involved in regulating cellular processes such as cell cycle, transcription, DNA repair, DNA damage response and chromatin remodeling. BRCA1 protein, located primarily in cell nuclei, interacts with multiple proteins and various DNA targets. It has been demonstrated that BRCA1 protein binds to damaged DNA and plays a role in the transcriptional regulation of downstream target genes. As a key protein in the repair of DNA double-strand breaks, the BRCA1-DNA binding properties, however, have not been reported in detail.

In this study, we provided detailed analyses of BRCA1 protein (DNA-binding domain, amino acid residues 444–1057) binding to topologically constrained non-B DNA structures (e.g. cruciform, triplex and quadruplex). Using electrophoretic retardation assay, atomic force microscopy and DNA binding competition assay, we showed the greatest preference of the BRCA1 DNA-binding domain to cruciform structure, followed by DNA quadruplex, with the weakest affinity to double stranded B-DNA and single stranded DNA. While preference of the BRCA1 protein to cruciform structures has been reported previously, our observations demonstrated for the first time a preferential binding of the BRCA1 protein also to triplex and quadruplex DNAs, including its visualization by atomic force microscopy.

Our discovery highlights a direct BRCA1 protein interaction with DNA. When compared to double stranded DNA, such a strong preference of the BRCA1 protein to cruciform and quadruplex structures suggests its importance in biology and may thus shed insight into the role of these interactions in cell regulation and maintenance.
Keyword BRCA1 protein
DNA binding
Protein-DNA complex
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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Sub-type: Article (original research)
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