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MBC in Press, published online ahead of print August 25, 2004
Mol. Biol. Cell 10.1091/mbc.E04-05-0436

A more recent version of this article appeared on November 1, 2004
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Submitted on May 28, 2004
Revised on August 11, 2004
Accepted on August 18, 2004

Nse1, Nse2, and a Novel Subunit of the Smc5-Smc6 Complex, Nse3, Play a Crucial Role in Meiosis

Stephanie Pebernard,* W. Hayes McDonald,{dagger} Yelena Pavlova,* John R. Yates III,{dagger} and Michael N. Boddy*{ddagger}

Departments of *Molecular Biology and {dagger}Cell Biology, The Scripps Research Institute, La Jolla, CA 92037

Monitoring Editor: Douglas Koshland

The structural maintenance of chromosomes (SMC) family of proteins play key roles in the organization, packaging and repair of chromosomes. Cohesin (Smc1 + 3) holds replicated sister chromatids together until mitosis, condensin (Smc2 + 4) acts in chromosome condensation and Smc5 + 6 performs currently enigmatic roles in DNA repair and chromatin structure. The SMC heterodimers must associate with nonSMC subunits to perform their functions. Using both biochemical and genetic methods we have isolated a novel subunit of the Smc5 + 6 complex, Nse3. Nse3 is an essential nuclear protein that is required for normal mitotic chromosome segregation and cellular resistance to a number of genotoxic agents. Epistasis with Rhp51 (Rad51) suggests that like Smc5 + 6, Nse3 functions in the homologous recombination based repair of DNA damage. We previously identified two nonSMC subunits of Smc5 + 6 called Nse1 and Nse2. Analysis of nse1-1, nse2-1 and nse3-1 mutants demonstrates that they are crucial for meiosis. The Nse1 mutant displays meiotic DNA segregation and homologous recombination defects. Spore viability is reduced by nse2-1 and nse3-1, without affecting interhomolog recombination. Finally, genetic interactions shared by the nse mutants suggest that the Smc5 + 6 complex is important for replication fork stability.

{ddagger}Corresponding author. E-mail: nboddy{at}scripps.edu






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