No matter which are the cause of the origin of the adducts, they are an obstacle for dividing cells, since they are blockers of replication and transcription. Several of them are active in more than one process. Although many DNA repair processes are rather well characterized in genomic non-replicated DNA, but during DNA replication, their roles are not so well understood. In this application, we focus on their interaction which is an area that has attracted a lot of interest although it is still not so well understood. We will focus on the role and interaction of different DNA repair proteins during DNA replication that has been blocked by the most sever lesions; a DNA-DNA inter strand a cross-link. Using that as a model we expect to find out novel principles for how repair proteins interact with the replication machinery, and further, through light over how molecules in DNA repair and molecules in DNA replication collaborate. Our preliminary data suggest that such interactions exist. Due to the fact that we have developed unique tools in addition the established ones, we believe that we can contribute to this field in a very significant way.