cra-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during c. elegans meiosiscra-1揭示一个双线break-dependent途径促进中部地区的组装蛋白质在秀丽隐杆线虫减数分裂染色体轴.pdfVIP

CRA-1 Uncovers a Double-Strand Break-Dependent Pathway Promoting the Assembly of Central Region Proteins on Chromosome Axes During C. elegans Meiosis ¨ ´ ´ Sarit Smolikov, Kristina Schild-Prufert, Monica P. Colaiacovo* Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America Abstract The synaptonemal complex (SC), a tripartite proteinaceous structure that forms between homologous chromosomes during meiosis, is crucial for faithful chromosome segregation. Here we identify CRA-1, a novel and conserved protein that is required for the assembly of the central region of the SC during C. elegans meiosis. In the absence of CRA-1, central region components fail to extensively localize onto chromosomes at early prophase and instead mostly surround the chromatin at this stage. Later in prophase, central region proteins polymerize along chromosome axes, but for the most part fail to connect the axes of paired homologous chromosomes. This defect results in an inability to stabilize homologous pairing interactions, altered double-strand break (DSB) repair progression, and a lack of chiasmata. Surprisingly, DSB formation and repair are required to promote the polymerization of the central region components along meiotic chromosome axes in cra- 1 mutants. In the absence of both CRA-1 and any one of the C. elegans homologs of SPO11, MRE11, RAD51, or MSH5, the polymerization observed along chromosome axes is perturbed, resulting in the formation of aggregates of the SC central region proteins. While radiation-induced DSBs rescue this polymerization in cra-1; spo-11 mutants, they fail to do so in cra-1; mre-11, cra-1; rad-51, and cra-1; msh-5 mutants. Taken together, our studies place CRA-1 as a key component in promoting the assembly of a