Characterization of DNA interstrand cross-link (ICL) repair in Saccharomyces cerevisiae has allowed us to determine that genes from all three epistasis groups of DNA repair [nucleotide excision repair, homologous recombination and post-replication/translesion repair] seem to encode proteins involved in this complex task. Although several of these genes had been identified, there has been little progress in clarifying the final steps of removal of an ICL from DNA.  We have investigated the relative roles in vivo of the yeast third subunit of DNA polymerase d (Pol d) Pol32, the subunit C of Pol e Dpb3 and the DNA polymerase a – binding protein Ctf4, in the removal of 8-methoxypsoralen photo-induced ICL. A yeast strain lacking subunit Pol32 of Pol d, is about 20 fold more sensitive to 8-MOP+UVA than its isogenic wild-type. This sensitivity phenotype was restricted to Pol d mutants, since neither the deletion of CTF4 nor of DPB3 genes resulted in increase of sensitivity to this photo-activated furocoumarin. Furthermore, using a plasmid transformation assay, we found that pol32D mutant is extremely deficient in joining incompatible DNA ends, particularly in cases of mismatched 5' overhangs, suggesting a role for DNA polymerase d in non-homologous end-joining (NHEJ). Sequencing of the recovered plasmids is under way to determine how the joints are generated in the pol32D mutant. Based on these findings we propose a model for removal of ICL from yeast DNA where the DSB, resulting from early steps in ICL processing, is subsequently repaired by DNA polymerase d-mediated NHEJ.