Premium
Deoxyribonucleotides as genetic and metabolic regulators
Author(s) -
Mathews Christopher K.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-251249
Subject(s) - deoxyribonucleotides , dna replication , deoxyribonucleotide , deoxyribonucleoside , replisome , biology , ribonucleotide reductase , dna synthesis , genetics , microbiology and biotechnology , dna , biochemistry , eukaryotic dna replication , nucleotide , gene , oligonucleotide , protein subunit
For > 35 yr, we have known that the accuracy of DNA replication is controlled in large part by the relative concentrations of the 4 canonical deoxyribonucleoside 5'‐triphosphates (dNTPs) at the replisome. Since this field was last reviewed, ~8 yr ago, there has been increased understanding of the mutagenic pathways as they occur in living cells. At the same time, aspects of deoxyribonucleotide metabolism have been shown to be critically involved in processes as diverse as cell cycle control, protooncogene expression, cellular defense against HIV infection, replication rate control, telomere length control, and mitochondrial function. Evidence supports a relationship between dNTP pools and microsatellite repeat instability. Relationships between dNTP synthesis and breakdown in controlling steady‐state pools have become better defined. In addition, new experimental approaches have allowed definitive analysis of mutational pathways induced by dNTP pool abnormalities, both in Escherichia coli and in yeast. Finally, ribonucleoside triphosphate (rNTP) pools have been shown to be critical determinants of DNA replication fidelity. These developments are discussed in this review article.—Mathews, C. K. Deoxyribonucleotides as genetic and metabolic regulators. FASEB J. 28, 3832‐3840 (2014). www.fasebj.org