Fanconi anemia (FA) is an inherited disease characterized by bone marrow 
failure, increased cancer risk and hypersensitivity to DNA cross-linking agents, 
implying a role for this pathway in the maintenance of genomic stability. The 
central player of the FA pathway is the multi-subunit E3 ubiquitin ligase 
complex activated through a replication- and DNA damage-dependent mechanism. A 
consequence of the activation of the complex is the monoubiquitylation of FANCD2 
and FANCI, late term effectors in the maintenance of genome integrity. The 
details regarding the coordination of the FA-dependent response and the DNA 
replication process are still mostly unknown. We found, by yeast two-hybrid 
assay and co-immunoprecipitation in human cells, that the core complex subunit 
FANCF physically interacts with PSF2, a member of the GINS complex essential for 
both the initiation and elongation steps of DNA replication. In HeLa cells 
depleted for PSF2, we observed a decreased binding to chromatin of the FA core 
complex, suggesting that the GINS complex may have a role in either loading or 
stabilizing the FA core complex onto chromatin. Consistently, GINS and core 
complex bind chromatin contemporarily upon origin firing and PSF2 depletion 
sensitizes cells to DNA cross-linking agents. However, depletion of PSF2 is not 
sufficient to reduce monoubiquitylation of FANCD2 or its localization to nuclear 
foci following DNA damage. Our results suggest a novel crosstalk between DNA 
replication and the FA pathway.