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Ribonucleotide Incorporation in Yeast Genomic DNA Shows Preference for Cytosine and Guanosine Preceded by Deoxyadenosine

Abstract

Despite the abundance of ribonucleoside monophosphates (rNMPs) in DNA, sites of rNMP incorporation remain poorly characterized. Here, by using ribose-seq and Ribose-Map techniques, we built and analyzed high-throughput sequencing libraries of rNMPs derived from mitochondrial and nuclear DNA of budding and fission yeast. We reveal both common and unique features of rNMP sites among yeast species and strains, and between wild type and different ribonuclease H-mutant genotypes. We demonstrate that the rNMPs are not randomly incorporated in DNA. We highlight signatures and patterns of rNMPs, including sites within trinucleotide-repeat tracts. Our results uncover that the deoxyribonucleotide immediately upstream of the rNMPs has a strong influence on rNMP distribution, suggesting a mechanism of rNMP accommodation by DNA polymerases as a driving force of rNMP incorporation. Consistently, we find deoxyadenosine upstream from the most abundant genomic rCMPs and rGMPs. This study establishes a framework to better understand mechanisms of rNMP incorporation in DNA.

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References
1.
Storici F, Bebenek K, Kunkel T, Gordenin D, Resnick M . RNA-templated DNA repair. Nature. 2007; 447(7142):338-41. PMC: 2121219. DOI: 10.1038/nature05720. View

2.
Clausen A, Zhang S, Burgers P, Lee M, Kunkel T . Ribonucleotide incorporation, proofreading and bypass by human DNA polymerase δ. DNA Repair (Amst). 2012; 12(2):121-7. PMC: 3552135. DOI: 10.1016/j.dnarep.2012.11.006. View

3.
Diamond T, Roshal M, Jamburuthugoda V, Reynolds H, Merriam A, Lee K . Macrophage tropism of HIV-1 depends on efficient cellular dNTP utilization by reverse transcriptase. J Biol Chem. 2004; 279(49):51545-53. PMC: 1351161. DOI: 10.1074/jbc.M408573200. View

4.
Chon H, Sparks J, Rychlik M, Nowotny M, Burgers P, Crouch R . RNase H2 roles in genome integrity revealed by unlinking its activities. Nucleic Acids Res. 2013; 41(5):3130-43. PMC: 3597693. DOI: 10.1093/nar/gkt027. View

5.
Gombolay A, Vannberg F, Storici F . Ribose-Map: a bioinformatics toolkit to map ribonucleotides embedded in genomic DNA. Nucleic Acids Res. 2018; 47(1):e5. PMC: 6326787. DOI: 10.1093/nar/gky874. View