Functional dissection of the Smc5/6 complex: roles of the SUMO ligase Nse2/Mms21 in the maintenance of genome stability
Kliszczak, Maciej
Kliszczak, Maciej
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http://hdl.handle.net/10379/2861
https://doi.org/10.13025/17917
https://doi.org/10.13025/17917
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2011-06
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Thesis
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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.
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Attribution-NonCommercial-NoDerivs 3.0 Ireland