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Smolikov, S; Schild-Prüfert, K; Colaiácovo, MP.
CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis.
PLoS Genet. 2008; 4(6): e1000088-e1000088. Doi: 10.1371/journal.pgen.1000088 [OPEN ACCESS]
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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 tripartite SC structure. Moreover, they reveal a scenario in which DSB formation and repair can drive the polymerization of SC components along chromosome axes in C. elegans.
Find related publications in this database (using NLM MeSH Indexing)
Amino Acid Sequence -
Animals -
Caenorhabditis elegans - cytology Caenorhabditis elegans - genetics Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - chemistry Caenorhabditis elegans Proteins - genetics Caenorhabditis elegans Proteins - metabolism
Chromosome Pairing -
Chromosomes - genetics
Crossing Over, Genetic -
DNA Breaks, Double-Stranded - radiation effects
Meiosis -
Molecular Sequence Data -
Mutation -
Protein Structure, Tertiary -
Sequence Alignment -
Synaptonemal Complex - genetics Synaptonemal Complex - metabolism

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