Differences in substrate specificity of C(5)-substituted or C(5)-unsubstituted pyrimidine nucleotides by DNA polymerases from thermophilic bacteria, archaea, and phages.
The pyrimidine bases of RNA are uracil (U) and cytosine (C), while thymine (T) and C are used for DNA. The C(5) position of C and U is unsubstituted, whereas the C(5) of T is substituted with a Me group. Miller et al. hypothesized that various C(5)-substituted uracil derivatives were formed during chemical evolution, and that C(5)-substituted U derivatives may have played important roles in the transition from an 'RNA world' to a 'DNA-RNA-protein world'. Hyperthermophilic bacteria and archaea are considered to be primitive organisms that are evolutionarily close to the universal ancestor of all life on earth. Thus, we examined the substrate specificity of several C(5)-substituted or C(5)-unsubstituted dUTP and dCTP analogs for several DNA polymerases from hyperthermophilic bacteria, hyperthermophilic archaea, and viruses during PCR or primer extension reaction. The substrate specificity of the C(5)-substituted or C(5)-unsubstituted pyrimidine nucleotides varied greatly depending on the type of DNA polymerase. The significance of this difference in substrate specificity in terms of the origin and evolution of the DNA replication system is discussed briefly.
Sawai
Hiroaki
H
Department of Applied Chemistry and Chemical Biology, Gunma University, Kiryu, Gunma 376-8515, Japan. sawai@chem.gunma-u.ac.jp
Nagashima
Junichi
J
Kuwahara
Msayasu
M
Kitagata
Rina
R
Tamura
Takehiro
T
Matsui
Ikuo
I
D001105:Archaea / Q000201:enzymology; D019843:Archaeal Proteins / Q000737:chemistry*; D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry*; D001435:Bacteriophages / Q000201:enzymology; D004247:DNA / Q000737:chemistry; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry*; D019143:Evolution, Molecular; D006358:Hot Temperature; D011742:Pyrimidine Nucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D013379:Substrate Specificity; D017361:Viral Nonstructural Proteins / Q000737:chemistry*
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D011742:Pyrimidine Nucleotides; D017361:Viral Nonstructural Proteins; D012313:RNA; D004247:DNA; D004259:DNA-Directed DNA Polymerase