The ubiquitination machinery of the Fanconi Anemia DNA repair pathway

The Fanconi Anemia (FA) pathway maintains genome stability by preventing DNA damage from occur-ring 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 phe-notypes 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. (c) 2020 Published by Elsevier Ltd.

Automated summary

The Fanconi Anemia (FA) pathway maintains genome stability by preventing DNA damage, with the FA core complex playing a central role in monoubiquitination of FANCI-FANCD2. Any mutations in the FA core complex can lead to defective monoubiquitination, resulting in various phenotypes including DNA damage sensitivity, birth defects, early-onset bone marrow failure, and cancer.