Structure-function analyses of mammalian Timeless in genome maintenance (10)

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Mammalian Timeless (Tim) and the Timeless-interacting protein (Tipin) are components of the replica-tion fork protection complex. To provide mechanistic insights into their functions in genome mainte-nance, we will analyse 3D structures of Tim, Tipin and their complexes with single-stranded DNA-binding RPA or DNA, using an integrated structural biology approach that includes X-ray crystallog-raphy, single particle cryo-electron microscopy, small angle X-ray scattering and crosslinking mass spectrometry. These studies will be complemented by cell-based in vivo functional analyses in order to advance our mechanistic understanding of replication stress signalling and fork protection.