Evolutionary Origins of DNA Repair Pathways: Role of Oxygen Catastrophe in the Emergence of DNA Glycosylases

Abstract

It was proposed that the last universal common ancestor (LUCA) evolved under high temperatures in an oxygen-free environment, similar to those found in deep-sea vents and on volcanic slopes. Therefore, spontaneous DNA decay, such as base loss and cytosine deamination, was the major factor affecting LUCA’s genome integrity. Cosmic radiation due to Earth’s weak magnetic field and alkylating metabolic radicals added to these threats. Here, we propose that ancient forms of life had only two distinct repair mechanisms: versatile apurinic/apyrimidinic (AP) endonucleases to cope with both AP sites and deaminated residues, and enzymes catalyzing the direct reversal of UV and alkylation damage. The absence of uracil–DNA N-glycosylases in some Archaea, together with the presence of an AP endonuclease, which can cleave uracil-containing DNA, suggests that the AP endonuclease-initiated nucleotide incision repair (NIR) pathway evolved independently from DNA glycosylase-mediated base excision repair. NIR may be a relic that appeared in an early thermophilic ancestor to counteract spontaneous DNA damage. We hypothesize that a rise in the oxygen level in the Earth’s atmosphere ~2 Ga triggered the narrow specialization of AP endonucleases and DNA glycosylases to cope efficiently with a widened array of oxidative base damage and complex DNA lesions.

Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer

“…The DDR encompasses different sensor and effector proteins, including exonucleases, that work together with the final aim of limiting damage, both for the cell and the organism. Almost all living organisms have evolved to possess a battery of mechanisms to ensure the preservation of their hereditary material, demonstrating the ubiquitous urgency to respond to damaged DNA [ 243 , 244 ]. DNA exonuclease activity is required for basic cell processes, such as the synthesis and repair of damaged DNA, cell death, and inflammation ( Figure 1 ) which are important to maintain homeostasis and prevent diseases and cancer.…”

The Evolution of Human Circadian Rhythms: An Ancient Defence Mechanism Impacting Modern Life-Styles

“…They possibly even function in magnetoreception 8 . The function of DNA repair has been taken over by nucleotide and base excision repair mechanisms that allow for repair of a wider range of DNA damage lesions 9,10,11 .…”

UV Radiation in DNA Damage and Repair Involving DNA-Photolyases and Cryptochromes

“…Cells have many different mechanisms for repairing each type of DNA damage that occurs spontaneously and is caused by exogenous factors [ 6 , 34 ]. The main mechanisms of DNA repair include: direct repair, when the enzyme restores the original structure without removing damaged nucleotides; excision repair, through the removal of damaged sites, followed by the synthesis of new nucleotides: base excision repair (BER) and nucleotide excision repair (NER); repair of unpaired bases (mismatch repair); repair of single-strand and double-strand breaks [ 6 , 34 ]. To remove photodamage, both direct repair with the participation of the DNA photolyase [ 4 , 35 , 36 ] and NER for CPD and (6-4)PP or BER for 8-OHdG [ 4 , 20 , 37 ] are used ( Figure 3 ).…”

“…The representatives of these three kingdoms have multiple differences in the repair mechanism. However, unlike photolyases, which are designed to remove only a limited type of damage, the NER system is able to remove a wide range of DNA damage, replacing not only photolyases but also BER if necessary [ 34 , 37 ]. The emergence of NER is believed to be the result of the response of living organisms to the complication of the biogenic chemosphere [ 34 ].…”

“…However, unlike photolyases, which are designed to remove only a limited type of damage, the NER system is able to remove a wide range of DNA damage, replacing not only photolyases but also BER if necessary [ 34 , 37 ]. The emergence of NER is believed to be the result of the response of living organisms to the complication of the biogenic chemosphere [ 34 ]. Multiple damaging factors appeared in the biogenic chemosphere, and they had to be removed by a more universal system, rather than inventing a separate removal system for each damage.…”