No abstract

The SMC5/6 complex is the least understood of SMC complexes. In yeast, smc5/6 mutants phenocopy mutations in sgs1, the BLM ortholog that is deficient in Bloom's syndrome (BS). We here show that NSMCE2 (Mms21, in Saccharomyces cerevisiae), an essential SUMO ligase of the SMC5/6 complex, suppresses cancer and aging in mice. Surprisingly, a mutation that compromises NSMCE2-dependent SUMOylation does not have a detectable impact on murine lifespan. In contrast, NSMCE2 deletion in adult mice leads to pathologies resembling those found in patients of BS. Moreover, and whereas NSMCE2 deletion does not have a detectable impact on DNA replication, NSMCE2-deficient cells also present the cellular hallmarks of BS such as increased recombination rates and an accumulation of micronuclei. Despite the similarities, NSMCE2 and BLM foci do not colocalize and concomitant deletion of Blm and Nsmce2 in B lymphocytes further increases recombination rates and is synthetic lethal due to severe chromosome mis-segregation. Our work reveals that SUMO-and BLM-independent activities of NSMCE2 limit recombination and facilitate segregation; functions of the SMC5/6 complex that are necessary to prevent cancer and aging in mice.

No abstract

This paper describes a method to measure the dynamic behavior of resist leaching in the time domain that is relevant for immersion lithography. The total leaching amount as a function of the contact time between water and resist is obtained and successfully fitted using previously described kinetic equations. In this way valuable information is obtained for the understanding of the contribution of resist leaching to lens contamination, CD uniformity and defectivity. The procedure is further used to study the effectiveness of various leaching mitigation strategies. Top coats prove to be a very effective method to reach the leaching specifications of the tool vendors. Also immersion dedicated resist materials meet the specifications or come very close.