Abstract:
Nse2/ Mms21 is an E3 SUMO ligase component of the Smc5/6 complex, which
plays multiple roles in maintaining genome stability. To study the functions of
the vertebrate Nse2 orthologue, we generated Nse2-deficient chicken DT40 cells.
Nse2 was dispensable for DT40 cell viability and required for efficient repair of
bulky DNA lesions, although double-strand break repair was unaffected.
Homologous recombination activities were reduced in Nse2-/-/- cells. Nse2
deficiency destabilised Smc5, but not Smc6. In rescue experiments, we found
that the SUMO ligase activity of Nse2 was required for an efficient response to
MMS-induced DNA damage, but not for Smc5 stability. Analysis of Nse2-/-/-
Smc5- clones, which were viable although slow-growing, showed that Smc5 and
Nse2 are not epistatic in DNA repair, suggesting that Smc5 and Nse2 have some
non-overlapping functions.
