A DNA repair interactome based on linear peptide motifs

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DNA present in our cells is continually being damaged in various ways and accordingly all known forms of life have evolved a complex set of biochemical pathways to detect and repair such damage, collectively called the DNA damage response. Like all biological pathways, the DNA damage response is facilitated by a series of protein-protein interactions, but the mechanisms by which DNA repair protein complexes are assembled, disassembled and regulated by post-translational modifications are still poorly understood. To address this issue, this project aims to develop and optimize a combined bioinformatics and proteomics approach to identify and characterize novel protein-protein interactions in DNA damage response proteins relying on conserved linear peptide motifs. Typically less than thirty amino acids in length, peptide motifs are recognised and/or post translationally modified by interacting partners. Historically, most research aiming to elucidate protein-protein interactions has focused on the interaction between the structured domains of proteins but in recent years it has become apparent that many interactions are mediated by peptide motifs. In addition to identifying novel protein-protein interactions, this method has potential to map these interactions to a specific region on one of those proteins and to gain insight into how this interaction is regulated if post-translational modifications are known to be present in the motif.