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Title:
Positive Selection Shapes Breast Cancer Tumor Suppressor Genes: Unveiling Insights into BRCA1, BRCA2, and MDC1 Stability | Journal of Molecular Evolution
Description:
Worldwide, breast cancer is the leading cause of death in women with cancers. Given this situation, new approaches to treatment are urgently needed. Tumor Suppressor Genes (TSGs) defects play a crucial role in tumor development, and recent studies propose their reactivation as a promising way for clinical intervention in breast cancer. Here, we performed detailed evolutionary analyses of 241 breast cancer TSGs across 25 mammalian genomes, revealing 28 genes under strong positive selection. These genes exhibit elevated molecular pressure in codons corresponding to amino acids located in crucial protein domains and motifs. Notably, one positively selected site in the BRCA1 C-terminal domain is known for its role in DNA damage response, suggesting potential interference with DNA repair mechanisms. Moreover, the substitution of some other sites found in important key motifs, namely two codons in BRCA2 (752 and 939) localized within the phosphoinositide-3-OH-kinase-related and playing a crucial role in the DNA repair and the DNA damage checkpoints. Our findings could be inspirational to foster future recommendations for drug-targeting sites and further illuminate the function of these proteins. Finally, the code developed in our study is delivered in the Automated tool for positive selection (ATPs) ( https://github.com/APS-P/Automated-Tool-for-Positive-Selection-ATPS-/wiki ) to assist the easy reproducibility and support future evolutionary genomics analyses.
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Keywords {🔍}
pubmed, article, google, scholar, cas, cancer, central, brca, genes, breast, acids, nucleic, evolution, res, molecular, dna, biol, analysis, selection, antunes, contributed, positive, tumor, mohamed, suppressor, emam, genome, ddd, data, role, access, gene, mol, evol, httpsdoiorgs, zhang, privacy, cookies, content, information, journal, publish, research, manuscript, fadel, khaled, agostinho, evolutionary, damage, repair,
Topics {✒️}
month download article/chapter sief el-din sobih tumor suppressor genes positive-selection-atps-/wiki projects ptdc/cta-amb/31774/2017 triple-negative breast cancer drug-targeting sites strategic funding u-idb/04423/2020 brca1 c-terminal domain full article pdf strong positive selection molecular evolution aims targeting mutant p53 biochim biophys acta neutral mutation hypothesis pan-tumor survey terminal de cruzeiros privacy choices/manage cookies symbiotic gene nork cancer genome landscapes ubiquitination/de-ubiquitination breast cancer deciding springer international publishing related subjects positively selected genes genes successfully targeted kauvar lm nucleic acids research human cancer genes breast cancer choices human genome adaptation positive selection breast cancer risk agostinho antunes contributed foster future recommendations breast cancer models writing—original draft molecular evolution tumor development porto de leixões comparative cellular response holds exclusive rights article log efficient cancer therapy utah state university article journal mohamed emam dna damage response writing—review & editing european economic area
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headline:Positive Selection Shapes Breast Cancer Tumor Suppressor Genes: Unveiling Insights into BRCA1, BRCA2, and MDC1 Stability
description:Worldwide, breast cancer is the leading cause of death in women with cancers. Given this situation, new approaches to treatment are urgently needed. Tumor Suppressor Genes (TSGs) defects play a crucial role in tumor development, and recent studies propose their reactivation as a promising way for clinical intervention in breast cancer. Here, we performed detailed evolutionary analyses of 241 breast cancer TSGs across 25 mammalian genomes, revealing 28 genes under strong positive selection. These genes exhibit elevated molecular pressure in codons corresponding to amino acids located in crucial protein domains and motifs. Notably, one positively selected site in the BRCA1 C-terminal domain is known for its role in DNA damage response, suggesting potential interference with DNA repair mechanisms. Moreover, the substitution of some other sites found in important key motifs, namely two codons in BRCA2 (752 and 939) localized within the phosphoinositide-3-OH-kinase-related and playing a crucial role in the DNA repair and the DNA damage checkpoints. Our findings could be inspirational to foster future recommendations for drug-targeting sites and further illuminate the function of these proteins. Finally, the code developed in our study is delivered in the Automated tool for positive selection (ATPs) (
https://github.com/APS-P/Automated-Tool-for-Positive-Selection-ATPS-/wiki
) to assist the easy reproducibility and support future evolutionary genomics analyses.
datePublished:2024-12-16T00:00:00Z
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Evolutionary analysis
Positive selection
Breast cancer
Drug targeting
Tumor suppressor genes
Evolutionary Biology
Microbiology
Plant Sciences
Plant Genetics and Genomics
Animal Genetics and Genomics
Cell Biology
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headline:Positive Selection Shapes Breast Cancer Tumor Suppressor Genes: Unveiling Insights into BRCA1, BRCA2, and MDC1 Stability
description:Worldwide, breast cancer is the leading cause of death in women with cancers. Given this situation, new approaches to treatment are urgently needed. Tumor Suppressor Genes (TSGs) defects play a crucial role in tumor development, and recent studies propose their reactivation as a promising way for clinical intervention in breast cancer. Here, we performed detailed evolutionary analyses of 241 breast cancer TSGs across 25 mammalian genomes, revealing 28 genes under strong positive selection. These genes exhibit elevated molecular pressure in codons corresponding to amino acids located in crucial protein domains and motifs. Notably, one positively selected site in the BRCA1 C-terminal domain is known for its role in DNA damage response, suggesting potential interference with DNA repair mechanisms. Moreover, the substitution of some other sites found in important key motifs, namely two codons in BRCA2 (752 and 939) localized within the phosphoinositide-3-OH-kinase-related and playing a crucial role in the DNA repair and the DNA damage checkpoints. Our findings could be inspirational to foster future recommendations for drug-targeting sites and further illuminate the function of these proteins. Finally, the code developed in our study is delivered in the Automated tool for positive selection (ATPs) (
https://github.com/APS-P/Automated-Tool-for-Positive-Selection-ATPS-/wiki
) to assist the easy reproducibility and support future evolutionary genomics analyses.
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Evolutionary analysis
Positive selection
Breast cancer
Drug targeting
Tumor suppressor genes
Evolutionary Biology
Microbiology
Plant Sciences
Plant Genetics and Genomics
Animal Genetics and Genomics
Cell Biology
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