Processing ribonucleotides incorporated during eukaryotic DNA replication.
The information encoded in DNA is influenced by the presence of non-canonical nucleotides, the most frequent of which are ribonucleotides. In this Review, we discuss recent discoveries about ribonucleotide incorporation into DNA during replication by the three major eukaryotic replicases, DNA polymerases α, δ and ε. The presence of ribonucleotides in DNA causes short deletion mutations and may result in the generation of single- and double-strand DNA breaks, leading to genome instability. We describe how these ribonucleotides are removed from DNA through ribonucleotide excision repair and by topoisomerase I. We discuss the biological consequences and the physiological roles of ribonucleotides in DNA, and consider how deficiencies in their removal from DNA may be important in the aetiology of disease.
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina 27709, USA.
Jessica S
JS
Williams
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina 27709, USA.
Scott A
SA
Lujan
Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina 27709, USA.
Thomas A
TA
Kunkel
D000818:Animals; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004260:DNA Repair; D004261:DNA Replication; D006801:Humans; D058105:Polymerization; D012265:Ribonucleotides / Q000378:metabolism*
D012265:Ribonucleotides; D004247:DNA