Figure 3.

SPTAN1 in DNA repair. SPTAN1 can translocate into the nucleus. In the nucleus, SPTAN1 can interact with various partners including proteins involved in DNA repair and fanconi anemia (FA). By binding FA proteins in nuclear complexes, SPTAN1 is stabilized and might act as scaffold to align or enhance DNA repair associated proteins at sites of damage. The FA protein FANCG (G) is able to bind to SPTAN1 through its SH3 domain. Via FANCA (A) and XPF, SPTAN1 enables DNA repair of interstrand crosslinks (ICLs). SPTAN1 circumvents telomere dysfunction after ICL damage by interaction with TRF1/2 and XPF. Furthermore, SPTAN1 can directly interact with MLH1, which mediates DNA mismatch repair (MMR). FANCJ, which is required for correction of the cross-link response, also interacts with the MMR complex MutLα, consisting of MLH1 and PMS2. A SPTAN1-dependent DNA repair mechanism, however, still remains unknown.