COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers

Rayka Yokoo; Karl A. Zawadzki; Kentaro Nabeshima; Melanie Drake; Swathi Arur; Anne M. Villeneuve

doi:10.1016/j.cell.2012.01.052

COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers

Rayka Yokoo, Karl A. Zawadzki, Kentaro Nabeshima, Melanie Drake, Swathi Arur, Anne M. Villeneuve

Genetics

Research output: Contribution to journal › Article › peer-review

173 Scopus citations

Abstract

Crossovers (COs) between homologous chromosomes ensure their faithful segregation during meiosis. We identify C. elegans COSA-1, a cyclin-related protein conserved in metazoa, as a key component required to convert meiotic double-strand breaks (DSBs) into COs. During late meiotic prophase, COSA-1 localizes to foci that correspond to the single CO site on each homolog pair and indicate sites of eventual concentration of other conserved CO proteins. Chromosomes gain and lose competence to load CO proteins during meiotic progression, with competence to load COSA-1 requiring prior licensing. Our data further suggest a self-reinforcing mechanism maintaining CO designation. Modeling of a nonlinear dose-response relationship between IR-induced DSBs and COSA-1 foci reveals efficient conversion of DSBs into COs when DSBs are limiting and a robust capacity to limit cytologically differentiated CO sites when DSBs are in excess. COSA-1 foci serve as a unique live cell readout for investigating CO formation and CO interference.

Original language	English (US)
Pages (from-to)	75-87
Number of pages	13
Journal	Cell
Volume	149
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2012.01.052
State	Published - Mar 30 2012

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2012.01.052

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@article{3ebe7b54036a403295aa4651962b300c,

title = "COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers",

abstract = "Crossovers (COs) between homologous chromosomes ensure their faithful segregation during meiosis. We identify C. elegans COSA-1, a cyclin-related protein conserved in metazoa, as a key component required to convert meiotic double-strand breaks (DSBs) into COs. During late meiotic prophase, COSA-1 localizes to foci that correspond to the single CO site on each homolog pair and indicate sites of eventual concentration of other conserved CO proteins. Chromosomes gain and lose competence to load CO proteins during meiotic progression, with competence to load COSA-1 requiring prior licensing. Our data further suggest a self-reinforcing mechanism maintaining CO designation. Modeling of a nonlinear dose-response relationship between IR-induced DSBs and COSA-1 foci reveals efficient conversion of DSBs into COs when DSBs are limiting and a robust capacity to limit cytologically differentiated CO sites when DSBs are in excess. COSA-1 foci serve as a unique live cell readout for investigating CO formation and CO interference.",

author = "Rayka Yokoo and Zawadzki, {Karl A.} and Kentaro Nabeshima and Melanie Drake and Swathi Arur and Villeneuve, {Anne M.}",

note = "Funding Information: We thank S. Mitani (National Institute of Genetics, Japan) and S. Rosu (Villeneuve lab) for cosa-1(tm3298) and zhp-3(me95); N. Bhalla, A. Dernburg, A. la Volpe, B. Meyer, S. Boulton, M. Zetka, and the Caenorhabditis Genetics Center for strains and antibodies; and J. Bessler for technical support. We thank A.D. Kaiser, M. AlQuaraishi, C. Janda, C. Thomas, D. Riordan, S. Clarke, and members of the Villeneuve lab for discussions and D. Libuda and A. Fire for comments on the manuscript. This work was supported by Stanford Genome Training Program NIH HG00044 Training Grant for R.Y., Leukemia and Lymphoma Society Postdoctoral Fellowship 5381-12 to K.A.Z., and NIH grant R01GM67268 to A.M.V. ",

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AU - Yokoo, Rayka

AU - Zawadzki, Karl A.

AU - Nabeshima, Kentaro

AU - Drake, Melanie

AU - Arur, Swathi

AU - Villeneuve, Anne M.

N1 - Funding Information: We thank S. Mitani (National Institute of Genetics, Japan) and S. Rosu (Villeneuve lab) for cosa-1(tm3298) and zhp-3(me95); N. Bhalla, A. Dernburg, A. la Volpe, B. Meyer, S. Boulton, M. Zetka, and the Caenorhabditis Genetics Center for strains and antibodies; and J. Bessler for technical support. We thank A.D. Kaiser, M. AlQuaraishi, C. Janda, C. Thomas, D. Riordan, S. Clarke, and members of the Villeneuve lab for discussions and D. Libuda and A. Fire for comments on the manuscript. This work was supported by Stanford Genome Training Program NIH HG00044 Training Grant for R.Y., Leukemia and Lymphoma Society Postdoctoral Fellowship 5381-12 to K.A.Z., and NIH grant R01GM67268 to A.M.V.

PY - 2012/3/30

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N2 - Crossovers (COs) between homologous chromosomes ensure their faithful segregation during meiosis. We identify C. elegans COSA-1, a cyclin-related protein conserved in metazoa, as a key component required to convert meiotic double-strand breaks (DSBs) into COs. During late meiotic prophase, COSA-1 localizes to foci that correspond to the single CO site on each homolog pair and indicate sites of eventual concentration of other conserved CO proteins. Chromosomes gain and lose competence to load CO proteins during meiotic progression, with competence to load COSA-1 requiring prior licensing. Our data further suggest a self-reinforcing mechanism maintaining CO designation. Modeling of a nonlinear dose-response relationship between IR-induced DSBs and COSA-1 foci reveals efficient conversion of DSBs into COs when DSBs are limiting and a robust capacity to limit cytologically differentiated CO sites when DSBs are in excess. COSA-1 foci serve as a unique live cell readout for investigating CO formation and CO interference.

AB - Crossovers (COs) between homologous chromosomes ensure their faithful segregation during meiosis. We identify C. elegans COSA-1, a cyclin-related protein conserved in metazoa, as a key component required to convert meiotic double-strand breaks (DSBs) into COs. During late meiotic prophase, COSA-1 localizes to foci that correspond to the single CO site on each homolog pair and indicate sites of eventual concentration of other conserved CO proteins. Chromosomes gain and lose competence to load CO proteins during meiotic progression, with competence to load COSA-1 requiring prior licensing. Our data further suggest a self-reinforcing mechanism maintaining CO designation. Modeling of a nonlinear dose-response relationship between IR-induced DSBs and COSA-1 foci reveals efficient conversion of DSBs into COs when DSBs are limiting and a robust capacity to limit cytologically differentiated CO sites when DSBs are in excess. COSA-1 foci serve as a unique live cell readout for investigating CO formation and CO interference.

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COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers

Abstract

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