DNA Damage Stress: Cui Prodest?

Nagendra Verma,Claudio Talora,Matteo Franchitto,Samantha Cialfi,Rocco Palermo,Azzurra Zonfrilli

doi:10.3390/ijms20051073

Nagendra Verma, Claudio Talora + Show 4 more

Open Access

https://doi.org/10.3390/ijms20051073

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Abstract

DNA is an entity shielded by mechanisms that maintain genomic stability and are essential for living cells; however, DNA is constantly subject to assaults from the environment throughout the cellular life span, making the genome susceptible to mutation and irreparable damage. Cells are prepared to mend such events through cell death as an extrema ratio to solve those threats from a multicellular perspective. However, in cells under various stress conditions, checkpoint mechanisms are activated to allow cells to have enough time to repair the damaged DNA. In yeast, entry into the cell cycle when damage is not completely repaired represents an adaptive mechanism to cope with stressful conditions. In multicellular organisms, entry into cell cycle with damaged DNA is strictly forbidden. However, in cancer development, individual cells undergo checkpoint adaptation, in which most cells die, but some survive acquiring advantageous mutations and selfishly evolve a conflictual behavior. In this review, we focus on how, in cancer development, cells rely on checkpoint adaptation to escape DNA stress and ultimately to cell death.

Highlights

While questionable, one of the most well-known and widely reported aspect in cancer biology is the acquisition of genetic mutations that underlie cell transformation and tumor progression
Cell transformation is a genetic process of tumor cells adapted to stressful environmental conditions; if to ‘cell adaptation’ can be conferred the Darwinian concept to respond to life’s needs for survival, the nature of what adaptation means for tumor cells is extremely elusive
This concept is suitable for viral carcinogenesis that hijacking cellular pathways promotes the survival and proliferation of infected cells, in a multicellular organism, cells do not need to adapt their phenotype to a non-permissive environment

Summary

Introduction

One of the most well-known and widely reported aspect in cancer biology is the acquisition of genetic mutations that underlie cell transformation and tumor progression. If we assess the concept that ‘adaptation’ means the optimization of the phenotype whereby the organism acquires changes that increase its survival and reproductive success, when this concept is applied to cell transformation it remains extremely vague This concept is suitable for viral carcinogenesis that hijacking cellular pathways promotes the survival and proliferation of infected cells, in a multicellular organism, cells do not need to adapt their phenotype to a non-permissive environment. Preservation of the integrity of multicellular organisms relies on these extra layers of developmental control that function to restrain cellular proliferation that may change in response to environmental or intracellular stress signals This implies that, as previously defined [6,7], cancer cells arise from cells adapted to respond to holistic control system and the escape from these host defense mechanisms represents an important strategy for cell transformation

Cell Cycle Surveillance System

After Event Cleaning Job

DNA Damage and the Balance between Survival and Death

Molecular Mechanisms of Checkpoint Adaptation

Consequences of Checkpoint Adaptation

Future Directions