To cope with ultraviolet C (UVC)-stalled replication forks and restart DNA 
synthesis, cells either undergo DNA translesion synthesis (TLS) by specialised 
DNA polymerases or tolerate the lesions using homologous recombination 
(HR)-based mechanisms. To gain insight into how cells manage UVC-induced stalled 
replication forks, we analysed the molecular crosstalk between the TLS DNA 
polymerases Polη and Rev1, the double-strand break repair (DSB)-associated 
protein MDC1 and the FANC pathway. We describe three novel functional 
interactions that occur in response to UVC-induced DNA lesions. First, Polη and 
Rev1, whose optimal expression and/or relocalisation depend on the FANC core 
complex, act upstream of FANCD2 and are required for the proper relocalisation 
of monoubiquitinylated FANCD2 (Ub-FANCD2) to subnuclear foci. Second, during 
S-phase, Ub-FANCD2 and MDC1 relocalise to UVC-damaged nuclear areas or foci 
simultaneously but independently of each other. Third, Ub-FANCD2 and MDC1 are 
independently required for optimal BRCA1 relocalisation. While RPA32 
phosphorylation (p-RPA32) and RPA foci formation were reduced in parallel with 
increasing levels of H2AX phosphorylation and MDC1 foci in UVC-irradiated FANC 
pathway-depleted cells, MDC1 depletion was associated with increased UVC-induced 
Ub-FANCD2 and FANCD2 foci as well as p-RPA32 levels and p-RPA32 foci. On the 
basis of the previous observations, we propose that the FANC pathway 
participates in the rescue of UVC-stalled replication forks in association with 
TLS by maintaining the integrity of ssDNA regions and by preserving genome 
stability and preventing the formation of DSBs, the resolution of which would 
require the intervention of MDC1.