InterPro domain: IPR029448

The Fanconi Anemia (FA) pathway is responsible for interstrand crosslink DNA repair [ 1 ]. The name originates the recessive syndrome known as Fanconi anemia, which causes developmental problems and cancer predisposition [ 2 ]. In this pathway, the FANCI-FANCD2 (ID) complex is ubiquitinated by the FA core complex and then travels to sites of damage to coordinate repair [ 3 , 4 ]. FA pathway activation seems to trigger dissociation of FANCD2 from FANCI, coinciding with FANCD2 monoubiquitination which precedes monoubiquitination of FANCI [ 5 ]. This suggests a functional separation for FANCD2 from FANCI [ 6 ].

Monoubiquitinated FANCD2 functions to recruit DNA repair factors FAN1 (Fanconi-associated nuclease 1) [ 7 ] and SLX4 [ 8 ], suggesting that chromatin-bound FANCD2Ub is a docking platform for certain DNA repair nucleases. FANCD2 has also a role in replication fork recovery [ 9 ].

1. Fanconi anemia pathway--the way of DNA interstrand cross-link repair. Pharmazie 68, 5-11
2. Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes. Int. J. Hematol. 74, 33-41
3. Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell 142, 77-88
4. Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2. Cell 142, 65-76
5. Fanconi anemia proteins FANCD2 and FANCI exhibit different DNA damage responses during S-phase. Nucleic Acids Res. 40, 8425-39
6. FANCD2 regulates BLM complex functions independently of FANCI to promote replication fork recovery. Nucleic Acids Res. 41, 6444-59
7. A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair. Mol. Cell 39, 36-47
8. Involvement of SLX4 in interstrand cross-link repair is regulated by the Fanconi anemia pathway. Proc. Natl. Acad. Sci. U.S.A. 108, 6492-6
9. CtIP mediates replication fork recovery in a FANCD2-regulated manner. Hum. Mol. Genet.