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The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction
SIMPLE SUMMARY: p53 is a nuclear transcription factor with a pro-apoptotic function. Somatic mutations in this gene represent one of the most critical events in human carcinogenesis. The disruption of genomic integrity due to the accumulation of various kinds of DNA damage, deficient DNA repair capa...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865496/ https://www.ncbi.nlm.nih.gov/pubmed/33513745 http://dx.doi.org/10.3390/cancers13030479 |
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author | Vodicka, Pavel Andera, Ladislav Opattova, Alena Vodickova, Ludmila |
author_facet | Vodicka, Pavel Andera, Ladislav Opattova, Alena Vodickova, Ludmila |
author_sort | Vodicka, Pavel |
collection | PubMed |
description | SIMPLE SUMMARY: p53 is a nuclear transcription factor with a pro-apoptotic function. Somatic mutations in this gene represent one of the most critical events in human carcinogenesis. The disruption of genomic integrity due to the accumulation of various kinds of DNA damage, deficient DNA repair capacity, and alteration of telomere homeostasis constitute the hallmarks of malignant diseases. The main aim of our review was to accentuate a complex comprehension of the interactions between fundamental players in carcinogenesis of solid malignancies such as DNA damage response, telomere homeostasis and TP53. ABSTRACT: The disruption of genomic integrity due to the accumulation of various kinds of DNA damage, deficient DNA repair capacity, and telomere shortening constitute the hallmarks of malignant diseases. DNA damage response (DDR) is a signaling network to process DNA damage with importance for both cancer development and chemotherapy outcome. DDR represents the complex events that detect DNA lesions and activate signaling networks (cell cycle checkpoint induction, DNA repair, and induction of cell death). TP53, the guardian of the genome, governs the cell response, resulting in cell cycle arrest, DNA damage repair, apoptosis, and senescence. The mutational status of TP53 has an impact on DDR, and somatic mutations in this gene represent one of the critical events in human carcinogenesis. Telomere dysfunction in cells that lack p53-mediated surveillance of genomic integrity along with the involvement of DNA repair in telomeric DNA regions leads to genomic instability. While the role of individual players (DDR, telomere homeostasis, and TP53) in human cancers has attracted attention for some time, there is insufficient understanding of the interactions between these pathways. Since solid cancer is a complex and multifactorial disease with considerable inter- and intra-tumor heterogeneity, we mainly dedicated this review to the interactions of DNA repair, telomere homeostasis, and TP53 mutational status, in relation to (a) cancer risk, (b) cancer progression, and (c) cancer therapy. |
format | Online Article Text |
id | pubmed-7865496 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78654962021-02-07 The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction Vodicka, Pavel Andera, Ladislav Opattova, Alena Vodickova, Ludmila Cancers (Basel) Review SIMPLE SUMMARY: p53 is a nuclear transcription factor with a pro-apoptotic function. Somatic mutations in this gene represent one of the most critical events in human carcinogenesis. The disruption of genomic integrity due to the accumulation of various kinds of DNA damage, deficient DNA repair capacity, and alteration of telomere homeostasis constitute the hallmarks of malignant diseases. The main aim of our review was to accentuate a complex comprehension of the interactions between fundamental players in carcinogenesis of solid malignancies such as DNA damage response, telomere homeostasis and TP53. ABSTRACT: The disruption of genomic integrity due to the accumulation of various kinds of DNA damage, deficient DNA repair capacity, and telomere shortening constitute the hallmarks of malignant diseases. DNA damage response (DDR) is a signaling network to process DNA damage with importance for both cancer development and chemotherapy outcome. DDR represents the complex events that detect DNA lesions and activate signaling networks (cell cycle checkpoint induction, DNA repair, and induction of cell death). TP53, the guardian of the genome, governs the cell response, resulting in cell cycle arrest, DNA damage repair, apoptosis, and senescence. The mutational status of TP53 has an impact on DDR, and somatic mutations in this gene represent one of the critical events in human carcinogenesis. Telomere dysfunction in cells that lack p53-mediated surveillance of genomic integrity along with the involvement of DNA repair in telomeric DNA regions leads to genomic instability. While the role of individual players (DDR, telomere homeostasis, and TP53) in human cancers has attracted attention for some time, there is insufficient understanding of the interactions between these pathways. Since solid cancer is a complex and multifactorial disease with considerable inter- and intra-tumor heterogeneity, we mainly dedicated this review to the interactions of DNA repair, telomere homeostasis, and TP53 mutational status, in relation to (a) cancer risk, (b) cancer progression, and (c) cancer therapy. MDPI 2021-01-27 /pmc/articles/PMC7865496/ /pubmed/33513745 http://dx.doi.org/10.3390/cancers13030479 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Vodicka, Pavel Andera, Ladislav Opattova, Alena Vodickova, Ludmila The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction |
title | The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction |
title_full | The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction |
title_fullStr | The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction |
title_full_unstemmed | The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction |
title_short | The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction |
title_sort | interactions of dna repair, telomere homeostasis, and p53 mutational status in solid cancers: risk, prognosis, and prediction |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865496/ https://www.ncbi.nlm.nih.gov/pubmed/33513745 http://dx.doi.org/10.3390/cancers13030479 |
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