The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

0552825 - ÚEM 2022 RIV CH eng J - Journal Article
Vodička, Pavel - Anděra, Ladislav - Opattová, Alena - Vodičková, Ludmila
The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction.
Cancers (Basel). Roč. 13, č. 2 (2021), č. článku 479. E-ISSN 2072-6694
R&D Projects: GA ČR(CZ) GA19-08772S; GA ČR(CZ) GA19-10543S
Institutional support: RVO:68378041 ; RVO:86652036
Keywords : interactions * DNA damage response * telomere homeostasis * TP53 mutational status * cancer risk * cancer progression * cancer therapy
OECD category: Genetics and heredity (medical genetics to be 3); Genetics and heredity (medical genetics to be 3) (BTO-N)
Impact factor: 6.575, year: 2021
Method of publishing: Open access
https://www.mdpi.com/2072-6694/13/3/479

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.

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.
Permanent Link: http://hdl.handle.net/11104/0327919