DNA crosslinking damage and cancer - a tale of friend and foe
Interstrand crosslinks (ICLs) represent a major challenge for DNA replication and transcription by preventing DNA strand separation. Cells deficient in ICL repair are hypersensitive to a variety of bifunctional alkylating agents and exhibit excessive genomic instability. Patients with deficient ICL repair, such as those with Fanconi anemia, are predisposed to a broad spectrum of cancers. The profound cellular toxicity of ICLs is exploited clinically in cancer chemotherapy. Therefore, understanding the mechanism of ICL repair and its impact on cancer development and treatment is very important. Studies of diseases with defective ICL repair, especially Fanconi anemia, have revealed unique ICL repair mechanisms in humans. In this review, we describe pathways and factors involved in ICL damage response and their implications in cancer development and treatment.