The Fanconi Anemia (FA) pathway maintains genome stability by preventing DNA damage from occurring when replication is blocked. Central to the FA pathway is the monoubiquitination of FANCI-FANCD2 mediated by a ubiquitin RING-E3 ligase complex called the FA core complex. Genetic mutation in any component of the FA core complex results in defective FANCI-FANCD2 monoubiquitination and phenotypes of DNA damage sensitivity, birth defects, early-onset bone marrow failure and cancer. Here, we discuss the mechanisms of the FA core complex and FANCI-FANCD2 monoubiquitination at sites of blocked replication and review our current understanding of the biological functions of these proteins in replication fork protection.
Keywords: DNA repair; FA core complex; FANCI-FANCD2; Fanconi anemia; Interstrand crosslink repair; Ubiquitination.
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