GRK 2243 "Understanding Ubiquitylation: From Molecular Mechanisms to Disease"

Project C1 (completed)

Role of USP28 in resolving transcription-replication conflicts

Markus Diefenbacher, Martin Eilers, Nikita Popov

Project C1 addresses a fundamental question in molecular biology: Both transcription and DNA replication use the same template strand, but often run in opposite directions. So how does a cell prevent collisions between an RNA polymerase and a replication fork? This is particularly relevant for understanding the biology of the MYC oncoproteins, since MYC proteins globally promote the release of RNA Polymerase from a promoter-proximal position (from where it can still be evicted) to an elongating state (where it is stably bound to DNA until the transcription end site). The project will analyze the mechanisms by which MYC-transformed tumor cells can escape transcription-replication conflicts and maintain genomic stability.