In mammalian cells, the enzymes of

In mammalian cells, the enzymes of thymidylate biosynthesis pathway are SUMOylated (covalently linked to the Small Ubiquitin-like MOdifier) during S-phase of the cell cycle and following DNA damage 5,8,9. This enables nuclear translocation of these enzymes, where they form a physical complex with nuclear lamin proteins and other enzymes of the DNA replication machinery (Figure 2).5 SHMT1 and SHMT2α are key enzymes in the complex, as they were shown to serve as scaffold proteins that tether the entire enzymatic complex to the nuclear lamina at sites of replication.5 Impairments in de novo thymidylate synthesis result in uracil misincorporation into DNA, which leads to single- and double-strand breaks during base-excision DNA repair.10