The Fanconi anemia pathway and ICL repair: implications for cancer therapy.
Fanconi anemia (FA) is an inherited disease caused by mutations in at least 13 genes and characterized by genomic instability. In addition to displaying strikingly heterogenous clinical phenotypes, FA patients are exquisitely sensitive to treatments with crosslinking agents that create interstrand crosslinks (ICL). In contrast to bacteria and yeast, in which ICLs are repaired through replication-dependent and -independent mechanisms, it is thought that ICLs are repaired primarily during DNA replication in vertebrates. However, recent data indicate that replication-independent ICL repair also operates in vertebrates. While the precise role of the FA pathway in ICL repair remains elusive, increasing evidence suggests that FA proteins function at different steps in the sensing, recognition and processing of ICLs, as well as in signaling from these very toxic lesions, which can be generated by a wide variety of cancer chemotherapeutic drugs. Here, we discuss some of the recent findings that have shed light on the role of the FA pathway in ICL repair, with special emphasis on the implications of these findings for cancer therapy since disruption of FA genes have been associated with cancer predisposition.
Wang
Lily C
LC
Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.
Gautier
Jean
J
D000818:Animals; D004260:DNA Repair; D004261:DNA Replication; D005199:Fanconi Anemia / Q000378:metabolism*; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction
D051856:Fanconi Anemia Complementation Group Proteins
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