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Review

G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency

by 1 and 1,2,*
1
Department of Biomedical Science, College of Life Science, CHA University, Sungnam 13488, Korea
2
Department of Pathology, CHA Bundang Medical Center, CHA University School of Medicine, Sungnam 13496, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Robert Winqvist
Genes 2022, 13(3), 391; https://doi.org/10.3390/genes13030391
Received: 6 January 2022 / Revised: 17 February 2022 / Accepted: 18 February 2022 / Published: 22 February 2022
(This article belongs to the Special Issue Advances in Genetics and Genomics of Ovarian Cancer)
How and why distinct genetic alterations, such as BRCA1 mutation, promote tumorigenesis in certain tissues, but not others, remain an important issue in cancer research. The underlying mechanisms may reveal tissue-specific therapeutic vulnerabilities. Although the roles of BRCA1, such as DNA damage repair and stalled fork stabilization, obviously contribute to tumor suppression, these ubiquitously important functions cannot explain tissue-specific tumorigenesis by BRCA1 mutations. Recent advances in our understanding of the cancer genome and fundamental cellular processes on DNA, such as transcription and DNA replication, have provided new insights regarding BRCA1-associated tumorigenesis, suggesting that G-quadruplex (G4) plays a critical role. In this review, we summarize the importance of G4 structures in mutagenesis of the cancer genome and cell type-specific gene regulation, and discuss a recently revealed molecular mechanism of G4/base excision repair (BER)-mediated transcriptional activation. The latter adequately explains the correlation between the accumulation of unresolved transcriptional regulatory G4s and multi-level genomic alterations observed in BRCA1-associated tumors. In summary, tissue-specific tumorigenesis by BRCA1 deficiency can be explained by cell type-specific levels of transcriptional regulatory G4s and the role of BRCA1 in resolving it. This mechanism would provide an integrated understanding of the initiation and development of BRCA1-associated tumors. View Full-Text
Keywords: BRCA1; G-quadruplex (G4); R-loop; tissue-specific-tumorigenesis; basal-like breast cancer; high-grade serous ovarian carcinoma (HGSC); BRCAness; oxidative genome damage; base excision repair BRCA1; G-quadruplex (G4); R-loop; tissue-specific-tumorigenesis; basal-like breast cancer; high-grade serous ovarian carcinoma (HGSC); BRCAness; oxidative genome damage; base excision repair
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MDPI and ACS Style

Kim, S.; Hwang, S. G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency. Genes 2022, 13, 391. https://doi.org/10.3390/genes13030391

AMA Style

Kim S, Hwang S. G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency. Genes. 2022; 13(3):391. https://doi.org/10.3390/genes13030391

Chicago/Turabian Style

Kim, Sanghyun, and Sohyun Hwang. 2022. "G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency" Genes 13, no. 3: 391. https://doi.org/10.3390/genes13030391

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