rNMP incorporation characteristics in eukaryotic genomic DNA
Ribonucleoside triphosphates (rNTPs) are incorporated into DNA by DNA polymerases in the form of ribonucleoside monophosphates (rNMPs), which are the most abundant non-standard nucleotides in genomic DNA in many species. The presence of rNMPs in DNA leads to DNA structural change, genome instability, and affects protein-DNA interactions. The rNMP incorporation is also associated with a bunch of human disease including Aicardi-Goutières Syndrome and various type of cancers. The incorporated rNTPs are mainly removed by the ribonucleotide excision repair (RER) pathway initiated by Ribonuclease (RNase) H2. Previous researchers already developed several rNMP-mapping techniques to capture the rNMPs in DNA at single nucleotide level. However, the analyses of rNTP incorporation are still limited to the basic study of rNMP counts and compositions in small genomes of RNase H2-deactivated cells. In this study, we aim to identify preferred rNTP-incorporation patterns, signatures, and hotspot motifs in the full genome of many eukaryotic cells including budding and fission yeast, green algae, and human cells. We hope our study can reveal the association between rNMP incorporation and vital biological processes including replication and transcription, and figure out the cellular function of rNMP incorporation.
- HHMI 55108574 Mechanisms of RNA-mediated genomic stability and instability, Howard Hughes Medical Institute Faculty Scholars Award (Francesca Storici, PI)
- R01 ES026243 Ribose-seq profile and analysis of ribonucleotides in DNA of oxidatively-stressed and cancer cells, _National Institute of Health (NIH) NIEHS (Francesca Storici, PI; Gianluca Tell, subcontract co-Investigator)
- AWD-002589 Decoding the cryptic language of ribonucleotide incorporation in human nuclear DNA, Mathers Foundation (Francesca Storici, PI)
- Deciphering the cryptic language of ribonucleotide incorporation in human nuclear DNA W. M. Keck Foundation (Francesca Storici, PI)