The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction
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 de...
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doaj-6aa0fde66eef4a2189f8dff6f83e9a762021-01-28T00:01:25ZengMDPI AGCancers2072-66942021-01-011347947910.3390/cancers13030479The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and PredictionPavel Vodicka0Ladislav Andera1Alena Opattova2Ludmila Vodickova3Institute of Experimental Medicine, AS CR, 142 20 Prague, Czech RepublicInstitute of Biotechnology, AS CR, 252 50 Vestec, Czech RepublicInstitute of Experimental Medicine, AS CR, 142 20 Prague, Czech RepublicInstitute of Experimental Medicine, AS CR, 142 20 Prague, Czech RepublicThe 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). <i>TP53</i>, the guardian of the genome, governs the cell response, resulting in cell cycle arrest, DNA damage repair, apoptosis, and senescence. The mutational status of <i>TP53</i> 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 <i>TP53</i>) 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 <i>TP53</i> mutational status, in relation to (a) cancer risk, (b) cancer progression, and (c) cancer therapy.https://www.mdpi.com/2072-6694/13/3/479interactionsDNA damage responsetelomere homeostasis<i>TP53</i> mutational statuscancer riskcancer progression |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pavel Vodicka Ladislav Andera Alena Opattova Ludmila Vodickova |
spellingShingle |
Pavel Vodicka Ladislav Andera Alena Opattova Ludmila Vodickova The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction Cancers interactions DNA damage response telomere homeostasis <i>TP53</i> mutational status cancer risk cancer progression |
author_facet |
Pavel Vodicka Ladislav Andera Alena Opattova Ludmila Vodickova |
author_sort |
Pavel Vodicka |
title |
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_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_sort |
interactions of dna repair, telomere homeostasis, and p53 mutational status in solid cancers: risk, prognosis, and prediction |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-01-01 |
description |
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). <i>TP53</i>, the guardian of the genome, governs the cell response, resulting in cell cycle arrest, DNA damage repair, apoptosis, and senescence. The mutational status of <i>TP53</i> 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 <i>TP53</i>) 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 <i>TP53</i> mutational status, in relation to (a) cancer risk, (b) cancer progression, and (c) cancer therapy. |
topic |
interactions DNA damage response telomere homeostasis <i>TP53</i> mutational status cancer risk cancer progression |
url |
https://www.mdpi.com/2072-6694/13/3/479 |
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