Nse1, Nse2, and a novel subunit of the Smc5-Smc6 complex, Nse3, play a crucial role in meiosis.
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 non-SMC 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 non-SMC 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.
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Stephanie
S
Pebernard
W Hayes
WH
McDonald
Yelena
Y
Pavlova
John R
JR
Yates
Michael N
MN
Boddy
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002875:Chromosomes / Q000648:ultrastructure; D004260:DNA Repair; D005720:Gamma Rays; D017353:Gene Deletion; D015151:Immunoblotting; D047468:Immunoprecipitation; D008540:Meiosis; D008938:Mitosis; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D012568:Schizosaccharomyces / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C460369:NSE1 protein, S cerevisiae; C498869:Nse1 protein, S pombe; C479823:Nse2 protein, S pombe; C495159:Nse3 protein, S pombe; D009687:Nuclear Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C486628:Smc5 protein, S pombe; C486630:smc6 protein, S pombe