Transcription factor binding to DNA mismatches – a potential driver of increased mutagenesis at regulatory sites: a QBI online seminar with Raluca Gordan

The QBI Online Seminar Series is presenting Raluca Gordan, an associate professor in the Center for Genomic and Computational Biology at Duke University. She received her PhD degree from Duke University in 2009, followed by postdoctoral training at the Harvard Medical School. Since 2011, the Gordan lab has been developing quantitative assays and mechanistic models to investigate how transcription factors interact with their genomic targets, how they compete/cooperate with one another, and more recently how they interact with DNA damage and repair. This research is funded by NIH, NSF, BSF, foundation awards (Sloan, PhRMA, March of Dimes, IDT), and Duke University.

A hyper-mutation pattern was recently observed at human transcription factor (TF) binding sites, over a wide range of proteins and cancer types, prompting the hypothesis that TFs contribute to mutagenesis by binding to DNA lesions and interfering with repair. However, little is known about how TFs interact with DNA lesions. In her talk, Dr. Gordan will discuss results showing widespread, high-affinity binding of TFs to DNA mismatches (i.e. non-complementary base-pairs resulting from replication errors). Her lab's new data reveal a critical role for conformational penalties in TF-DNA recognition, and suggest that TFs can compete with mismatch repair enzymes, thus potentially elevating mutagenesis at regulatory sites.