Mechanism and implications of ribonucleotide incorporation into DNA

Current projects in our group focus on the following:

1. Genome-wide mapping of ribonucleotides in DNA.
More than a million ribonucleotides are incorporated into the human genome per round of replication. We are interested in the causes and consequences of these ribonucleotides in our genome. We study where those ribonucleotides are incorporated in a number of model organisms including virus, yeast, mice and human. A number of pathways may be involved in removing these ribonucleotides. We analyze if ribonucleotides are differentially incorporated in various mutants that lack specific genes which codes for proteins that may be involved in the processing or removal of ribonucleotides in DNA.

2. Development of new methods to map genome-wide ribonucleotides in DNA.
Based on our recently developed HydEn-seq protocol to genome-wide map ribonucleotides in DNA, we continue to improve and develop tools to study where ribonucleotides are incorporated into our genome. We expect that a better understanding of how ribonucleotides in DNA contribute to genome stability and instability will ultimately impact biomedical science.

3. Genome-wide tracking of DNA polymerases.
We also investigate where specific DNA polymerases take part in synthesizing the genome by mapping ribonucleotides incorporated by various steric gate variants of DNA polymerases as outlined in (Clausen et al, Nat Struct Mol Biol. 2015 Mar; 22(3): 185–191.) We track DNA polymerases from both bacteria, yeast and other eukaryotes.