title: DNA interstrand cross-link repair: understanding role of Fanconi anemia pathway and therapeutic implications.
abstract: Interstrand cross-links (ICLs) are extremely toxic DNA lesions that prevent DNA double-helix separation due to the irreversible covalent linkage binding of some agents on DNA strands. Agents that induce these ICLs are thus widely used as chemotherapeutic drugs but may also lead to tumor growth. Fanconi anemia (FA) is a rare genetic disorder that leads to ICL sensitivity. This review provides update on current understanding of the role of FA proteins in repairing ICLs at various stages of cell cycle. We also discuss link between DNA cross-link genotoxicity caused by aldehydes in FA pathway. Besides this, we summarize various ICL agents that act as drugs to treat different types of tumors and highlight strategies for modulating ICL sensitivity for therapeutic interventions that may be helpful in controlling cancer and life-threatening disease, FA.
authors.affiliation: Department of Cytogenetics, National Institute of Immunohaematology (NIIH), Mumbai, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Shukla
authors.forename: Avani
authors.initials: A
authors.lastname: Solanki
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Babu Rao
authors.initials: BR
authors.lastname: Vundinti
mesh_terms: D001388:Aziridines / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair; D005199:Fanconi Anemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009588:Nitrogen Mustard Compounds / Q000737:chemistry / Q000494:pharmacology; D017671:Platinum Compounds / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D001388:Aziridines; D003432:Cross-Linking Reagents; D051856:Fanconi Anemia Complementation Group Proteins; D009588:Nitrogen Mustard Compounds; D017671:Platinum Compounds
keywords: Fanconi anemia; cancer; chemotherapy; interstrand cross-links