Mammalian Timeless (Tim) and the Timeless-interacting protein (Tipin) are components of the replication fork protection complex. To provide mechanistic insights into their functions in genome maintenance, we will analyse 3D structures of Tim, Tipin and their complexes with the single-stranded DNA-binding protein RPA (replication protein A) or with DNA. We will use an integrated structural biology approach that includes X-ray crystallography, single particle cryo-electron microscopy (cryo-EM), small angle X-ray scattering (SAXS) and crosslink mass spectrometry analyses. These studies will be complemented by cell-based in vivo functional analyses in order to advance our mechanistic understanding of replication stress signaling and fork protection.
Structure-function analyses of mammalian Timeless in genome maintenance