Abstract
The abundance of ribonucleotides in DNA remained undetected until recently because they are efficiently removed by the ribonucleotide excision repair (RER) pathway, a process similar to Okazaki fragment (OF) processing after incision by Ribonuclease H2 (RNase H2). All DNA polymerases incorporate ribonucleotides during DNA synthesis. How many, when, and why they are incorporated has been the focus of intense work during recent years by many labs. In this review, we discuss recent advances in ribonucleotide incorporation by eukaryotic DNA polymerases that suggest an evolutionarily conserved role for ribonucleotides in DNA. We also review the data that indicate that removal of ribonucleotides has an important role in maintaining genome stability.
Keywords:
Aicardi–Goutières syndrome; DNA polymerase; RER; RNase H2; steric gate; systemic lupus erythematosus.
Published by Elsevier Ltd.
MeSH terms
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Animals
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Archaeoglobus fulgidus / genetics
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Archaeoglobus fulgidus / metabolism
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Autoimmune Diseases of the Nervous System / genetics*
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Autoimmune Diseases of the Nervous System / metabolism
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Autoimmune Diseases of the Nervous System / pathology
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DNA / genetics
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DNA / metabolism*
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DNA Repair*
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DNA Replication
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DNA-Directed DNA Polymerase / genetics
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DNA-Directed DNA Polymerase / metabolism
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism
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Genomic Instability
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Humans
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Lupus Erythematosus, Systemic / genetics*
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Lupus Erythematosus, Systemic / metabolism
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Lupus Erythematosus, Systemic / pathology
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Mutation
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Nervous System Malformations / genetics*
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Nervous System Malformations / metabolism
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Nervous System Malformations / pathology
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Nucleosomes / genetics
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Nucleosomes / metabolism
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Nucleosomes / ultrastructure
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Ribonuclease H / chemistry
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Ribonuclease H / genetics*
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Ribonuclease H / metabolism
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Ribonucleotides / genetics
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Ribonucleotides / metabolism*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
Substances
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Nucleosomes
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Ribonucleotides
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DNA
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DNA-Directed DNA Polymerase
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ribonuclease HII
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Ribonuclease H
Supplementary concepts
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Aicardi-Goutieres syndrome