a new thermosensitive smc-3 allele reveals involvement of cohesin in homologous recombination in c. elegans一个新的热敏的smc-3等位基因显示cohesin参与同源重组在秀丽隐杆线虫.pdfVIP

A New Thermosensitive smc-3 Allele Reveals Involvement of Cohesin in Homologous Recombination in C. elegans 1 1 1 1 1 Antoine Baudrimont , Alexandra Penkner , Alexander Woglar , Yasmine M. Mamnun , Margot Hulek , 2 2 1 1 Cathrin Struck , Ralf Schnabel , Josef Loidl , Verena Jantsch * 1 Max F. Perutz Laboratories, Department of Chromosome Biology, University of Vienna, Vienna, Austria, 2 Department of Genetics, Technical University of Braunschweig, Braunschweig, Germany Abstract The cohesin complex is required for the cohesion of sister chromatids and for correct segregation during mitosis and meiosis. Crossover recombination, together with cohesion, is essential for the disjunction of homologous chromosomes during the first meiotic division. Cohesin has been implicated in facilitating recombinational repair of DNA lesions via the sister chromatid. Here, we made use of a new temperature-sensitive mutation in the Caenorhabditis elegans SMC-3 protein to study the role of cohesin in the repair of DNA double-strand breaks (DSBs) and hence in meiotic crossing over. We report that attenuation of cohesin was associated with extensive SPO-11–dependent chromosome fragmentation, which is representative of unrepaired DSBs. We also found that attenuated cohesin likely increased the number of DSBs and eliminated the need of MRE-11 and RAD-50 for DSB formation in C. elegans, which suggests a role for the MRN complex in making cohesin-loaded chromatin susceptible to meiotic DSBs. Notably, in spite of largely intact sister chromatid cohesion, backup DSB repair via the sister chromatid wa