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-Prüfert; Mónica P Colaiácovo

doi:10.1371/journal.pgen.1000088

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CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis

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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-Prüfert and Mónica P Colaiácovo

PLoS genetics, Vol.4(6), pp.e1000088-e1000088

06/06/2008

DOI: 10.1371/journal.pgen.1000088

PMCID: PMC2408554

PMID: 18535664

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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.

Protein Structure, Tertiary

Amino Acid Sequence

Caenorhabditis elegans - metabolism

Crossing Over, Genetic

Caenorhabditis elegans - genetics

Caenorhabditis elegans Proteins - chemistry

Caenorhabditis elegans Proteins - metabolism

Molecular Sequence Data

Meiosis

Synaptonemal Complex - genetics

DNA Breaks, Double-Stranded - radiation effects

Synaptonemal Complex - metabolism

Sequence Alignment

Animals

Caenorhabditis elegans - cytology

Chromosomes - genetics

Mutation

Caenorhabditis elegans Proteins - genetics

Chromosome Pairing

Details

Title: Subtitle: CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis
Creators: Sarit Smolikov - Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
Kristina Schild-Prüfert
Mónica P Colaiácovo
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.4(6), pp.e1000088-e1000088
DOI: 10.1371/journal.pgen.1000088
PMID: 18535664
PMCID: PMC2408554
NLM abbreviation: PLoS Genet
ISSN: 1553-7390
eISSN: 1553-7404
Publisher: United States
Grant note: R01GM072551 / NIGMS NIH HHS\nR01 GM072551 / NIGMS NIH HHS
Language: English
Date published: 06/06/2008
Academic Unit: Biology
Record Identifier: 9983991957602771

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