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G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency
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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948836/ https://www.ncbi.nlm.nih.gov/pubmed/35327946 http://dx.doi.org/10.3390/genes13030391 |
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author | Kim, Sanghyun Hwang, Sohyun |
author_facet | Kim, Sanghyun Hwang, Sohyun |
author_sort | Kim, Sanghyun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8948836 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89488362022-03-26 G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency Kim, Sanghyun Hwang, Sohyun Genes (Basel) Review 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. MDPI 2022-02-22 /pmc/articles/PMC8948836/ /pubmed/35327946 http://dx.doi.org/10.3390/genes13030391 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Kim, Sanghyun Hwang, Sohyun G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency |
title | G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency |
title_full | G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency |
title_fullStr | G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency |
title_full_unstemmed | G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency |
title_short | G-Quadruplex Matters in Tissue-Specific Tumorigenesis by BRCA1 Deficiency |
title_sort | g-quadruplex matters in tissue-specific tumorigenesis by brca1 deficiency |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948836/ https://www.ncbi.nlm.nih.gov/pubmed/35327946 http://dx.doi.org/10.3390/genes13030391 |
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