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.
Highlights
This theoretical essay was inspired by Miroslav Radman’s works on the mechanisms of SOS response and mismatch repair in bacteria
We propose that last universal common ancestor (LUCA) employed a photolyase and O6alkylguanine alkyl transferase to repair UV and alkylation DNA damage, respectively, whereas spontaneous DNA decay and ionizing radiation-induced DNA damage were counteracted by the nucleotide incision repair (NIR)-specific AP endonucleases, AP lyases and 30 -repair phosphodiesterases (Figure 1B–F)
Unlike the HhH motif, it is found only in a limited group of polypeptides, including ribosomal protein S13 (S18 in eukaryotes) and several ribosome quality control proteins. These glycosylases carry a DNA-binding β-ribbon zinc finger or a structurally equivalent β2 -module called a “zincless finger”, and a unique N-terminal β-sandwich domain with the catalytic N-terminal amino group and a catalytic acidic side chain [133,134]. Members of this group are missing from Archaea, and, as they are exclusively involved in oxidative damage repair, the H2tH glycosylases represent good candidates for acquisition from symbiotic mitochondria functionally associated with the evolution of oxidative metabolism
Summary
This theoretical essay was inspired by Miroslav Radman’s works on the mechanisms of SOS response and mismatch repair in bacteria. Perhaps the first phylogenomic analysis of DNA repair proteins, based on a limited set of the complete genome sequences, was performed by Eisen and Hanawalt, who made predictions about the repair phenotypes and offered important insights into the evolution of whole pathways [1] They suggested that photolyases, alkyltransferases, Xth/Nfo. AP endonucleases and MutY/Nth DNA glycosylases are very ancient enzymes and were present in the common ancestor, whereas the NER pathway had different origins in bacteria and eukaryotes/archaea. We propose that the DNA glycosylase-initiated BER and multi-protein complex mediated NER systems appeared later in evolution, offering more versatile and efficient catalytic mechanisms that involve sequential actions of several repair proteins to remove DNA damage and generate a single-stranded gap of varying length with a proper 30 -end that can be used as a primer for DNA repair synthesis and ligation (Figure 1G,H,J). We propose that LUCA employed a photolyase and O6alkylguanine alkyl transferase to repair UV and alkylation DNA damage, respectively, whereas spontaneous DNA decay and ionizing radiation-induced DNA damage were counteracted by the NIR-specific AP endonucleases, AP lyases and 30 -repair phosphodiesterases (Figure 1B–F)
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