Limits...
The origin and evolution of ribonucleotide reduction.

Lundin D, Berggren G, Logan DT, Sjöberg BM - Life (Basel) (2015)

Bottom Line: Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms.This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR).While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR).

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. daniel.lundin@scilifelab.se.

ABSTRACT
Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms. This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR). The mechanism has been deemed unlikely to be catalyzed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesized at the transition from RNA- to DNA-encoded genomes. While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to modern RNRs, the urRNR, which diversified into the modern three classes. Since the initial radical generation differs between the three modern classes, it is difficult to establish how it was generated in the urRNR. Here we suggest a model that is similar to the B12-dependent mechanism in modern class II RNRs.

No MeSH data available.


The transition from the RNA world to the RNP world and, by the action of the protoRNR, to the modern RNA + protein + DNA world. Evolutionary novelties are marked in bold blue text. Whereas non-redox active divalent metals in ribozymes are common, metals catalyzing electron transfer in ribozymes are much more rare (see main text).
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life-05-00604-f002: The transition from the RNA world to the RNP world and, by the action of the protoRNR, to the modern RNA + protein + DNA world. Evolutionary novelties are marked in bold blue text. Whereas non-redox active divalent metals in ribozymes are common, metals catalyzing electron transfer in ribozymes are much more rare (see main text).

Mentions: The stage for our model is one where the first steps from a pure RNA world (see [5] for a recent review) towards an RNP world have been taken. We assume translated proteins have originated, acting as assembly points for redox-active metals as well as RNA world cofactors (ribonucleoside-derived carbon radicals). Besides working as assembly points, proteins isolate cleavage-sensitive RNAs from strong redox-potentials in metals and organic radicals (Figure 2).


The origin and evolution of ribonucleotide reduction.

Lundin D, Berggren G, Logan DT, Sjöberg BM - Life (Basel) (2015)

The transition from the RNA world to the RNP world and, by the action of the protoRNR, to the modern RNA + protein + DNA world. Evolutionary novelties are marked in bold blue text. Whereas non-redox active divalent metals in ribozymes are common, metals catalyzing electron transfer in ribozymes are much more rare (see main text).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390871&req=5

life-05-00604-f002: The transition from the RNA world to the RNP world and, by the action of the protoRNR, to the modern RNA + protein + DNA world. Evolutionary novelties are marked in bold blue text. Whereas non-redox active divalent metals in ribozymes are common, metals catalyzing electron transfer in ribozymes are much more rare (see main text).
Mentions: The stage for our model is one where the first steps from a pure RNA world (see [5] for a recent review) towards an RNP world have been taken. We assume translated proteins have originated, acting as assembly points for redox-active metals as well as RNA world cofactors (ribonucleoside-derived carbon radicals). Besides working as assembly points, proteins isolate cleavage-sensitive RNAs from strong redox-potentials in metals and organic radicals (Figure 2).

Bottom Line: Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms.This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR).While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR).

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. daniel.lundin@scilifelab.se.

ABSTRACT
Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms. This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR). The mechanism has been deemed unlikely to be catalyzed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesized at the transition from RNA- to DNA-encoded genomes. While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to modern RNRs, the urRNR, which diversified into the modern three classes. Since the initial radical generation differs between the three modern classes, it is difficult to establish how it was generated in the urRNR. Here we suggest a model that is similar to the B12-dependent mechanism in modern class II RNRs.

No MeSH data available.