FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2

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Fanconi anemia is a genetic disease characterized by bone marrow failure, congenital malformations and cancer predisposition. Cells derived from Fanconi anemia patients have a dysfunctional FA-BRCA pathway and are deficient in the repair of a specific form of DNA damage, DNA interstrand-crosslinks, that are induced by certain chemotherapeutic drugs. Therefore, the study of FA-BRCA pathway regulation is essential for developing new treatments for Fanconi anemia patients and cancer patients in general. One of the first steps in the pathway is the detection of DNA lesions by the FA core complex. We have optimized a method to visualize the recruitment of the FA core complex to sites of DNA damage and, for the first time, explored how this process occurs. We have uncovered several factors that are required for this recruitment. Among them is a FA core complex substrate, FANCI. We report that non-phosphorylated FANCI, previously believed to be an inactive form, has an important role in the recruitment of the FA core complex and DNA interstrand-crosslink repair. Our findings change the current view of the FA-BRCA pathway and have implications for potential clinical strategies aimed at activating or inhibiting the FA-BRCA pathway.

Vyšlo v časopise: FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005563
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005563

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