Repair of DNA interstrand cross-links

DNA interstrand cross-links (ICLs) are very toxic to dividing cells, becaus e they induce mutations, chromosomal rearrangements and cell death. Inducer s of ICLs are important drugs in cancer treatment. We discuss the main prop erties of several classes of ICL agents and the types of damage they induce . The current insights in ICL repair in bacteria, yeast and mammalian cells are reviewed. An intriguing aspect of ICLs is that a number of multi-step DNA repair pathways including nucleotide excision repair, homologous recomb ination and post-replication/translesion repair all impinge on their repair . Furthermore, the breast cancer-associated proteins Brca1 and Brca2, the F anconi anemia-associated FANC proteins, and cell cycle checkpoint proteins are involved in regulating the cellular response to ICLs. We depict several models that describe possible pathways for the repair or replicational byp ass of ICLs. (C) 2001 Elsevier Science B.V All rights reserved.