Description:

Title:

Genome Instability Caused by Persistent RNA-DNA Hybrid Formation

Spealer:

Lyle SImmons, PhD, Professor, University of Michigan, Department of Molecular, Cellular and Developmental Biology

Topic:

RNA-DNA hybrids form through DNA polymerase errors, Okazaki fragment primers, and as R-loops during transcription. Our lab has studied the effect of persistent ribonucleotides on genome integrity, using a combination of mutation accumulation lines, genetics, and in vitro reconstitution experiments. We have found that persistent ribonucleotide insertion leads to increased mutagenesis through an error-prone resynthesis pathway. Our work also shows that elevated R-loops cause gross chromosomal rearrangements and perturbations to DNA replication. Failure to properly resolve RNA-DNA hybrids results in slower growth and the acquisition of mutations that can lead to antibiotic resistance.

Host:

Hank Seifert, PhD, Professor, Dept. of Microbiology-Immunology