Repair of DNA interstrand cross-links during S phase of the mammalian cell cycle

DNA interstrand cross-linking (ICL) agents are widely used in anticancer chemotherapy regimens, yet our understanding of the DNA repair mechanisms by which these lesions are removed from the genome remains incomplete. This is at least in part due to the enormously complicated nature and variety of the biochemical pathways that operate on these complex lesions. In this review, we have focused specifically on the S-phase pathway of ICL repair in mammalian cells, which appears to be the major mechanism by which these lesions are removed in cycling cells. The various stages and components of this pathway are discussed, and a putative molecular model is presented. In addition, we propose an explanation as to how this pathway can lead to the observed high levels of sister chromatid exchanges known to be induced by ICLs.