All Publications


  • Disparate roles for C. elegans DNA translocase paralogs RAD-54.L and RAD-54.B in meiotic prophase germ cells. Nucleic acids research Yamaya, K., Wang, B., Memar, N., Odiba, A. S., Woglar, A., Gartner, A., Villeneuve, A. M. 2023

    Abstract

    RAD54 family DNA translocases partner with RAD51 recombinases to ensure stable genome inheritance, exhibiting biochemical activities both in promoting recombinase removal and in stabilizing recombinase association with DNA. Understanding how such disparate activities of RAD54 paralogs align with their biological roles is an ongoing challenge. Here we investigate the in vivo functions of Caenorhabditis elegans RAD54 paralogs RAD-54.L and RAD-54.B during meiotic prophase, revealing distinct contributions to the dynamics of RAD-51 association with DNA and to the progression of meiotic double-strand break repair (DSBR). While RAD-54.L is essential for RAD-51 removal from meiotic DSBR sites to enable recombination progression, RAD-54.B is largely dispensable for meiotic DSBR. However, RAD-54.B is required to prevent hyperaccumulation of RAD-51 on unbroken DNA during the meiotic sub-stage when DSBs and early recombination intermediates form. Moreover, DSB-independent hyperaccumulation of RAD-51 foci in the absence of RAD-54.B is RAD-54.L-dependent, revealing a hidden activity of RAD-54.L in promoting promiscuous RAD-51 association that is antagonized by RAD-54.B. We propose a model wherein a division of labor among RAD-54 paralogs allows germ cells to ramp up their capacity for efficient homologous recombination that is crucial to successful meiosis while counteracting potentially deleterious effects of unproductive RAD-51 association with unbroken DNA.

    View details for DOI 10.1093/nar/gkad638

    View details for PubMedID 37548405

  • A new partial loss of function allele of rad-54.L. microPublication biology Akerib, C. C., Yokoo, R., Nsamba, E. T., Strand, L. G., Yamaya, K., Villeneuve, A. M. 2022; 2022

    Abstract

    RAD-54.L is required for the repair of meiotic double-strand DNA breaks (DSBs), playing an essential role in promoting removal of recombinase RAD-51 and normal completion of meiotic recombination. Failure to complete meiotic DSB repair leads to 100% lethality of embryos produced by rad-54.L null mutant mothers. Here we report a new partial loss of function allele, rad-54.L(me139) , that may prove useful for investigating meiotic mechanisms by providing a sensitized genetic background that reduces but does not eliminate the essential functions of RAD-54.L.

    View details for DOI 10.17912/micropub.biology.000637

    View details for PubMedID 36247323

  • Caenorhabditis elegans DSB-3 reveals conservation and divergence among protein complexes promoting meiotic double-strand breaks PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Hinman, A. W., Yeh, H., Roelens, B., Yamaya, K., Woglar, A., Bourbon, H. G., Chi, P., Villeneuve, A. M. 2021; 118 (33)
  • Quantitative cytogenetics reveals molecular stoichiometry and longitudinal organization of meiotic chromosome axes and loops. PLoS biology Woglar, A. n., Yamaya, K. n., Roelens, B. n., Boettiger, A. n., K√∂hler, S. n., Villeneuve, A. M. 2020; 18 (8): e3000817

    Abstract

    During meiosis, chromosomes adopt a specialized organization involving assembly of a cohesin-based axis along their lengths, with DNA loops emanating from this axis. We applied novel, quantitative, and widely applicable cytogenetic strategies to elucidate the molecular bases of this organization using Caenorhabditis elegans. Analyses of wild-type (WT) chromosomes and de novo circular minichromosomes revealed that meiosis-specific HORMA-domain proteins assemble into cohorts in defined numbers and co-organize the axis together with 2 functionally distinct cohesin complexes (REC-8 and COH-3/4) in defined stoichiometry. We further found that REC-8 cohesins, which load during S phase and mediate sister-chromatid cohesion, usually occur as individual complexes, supporting a model wherein sister cohesion is mediated locally by a single cohesin ring. REC-8 complexes are interspersed in an alternating pattern with cohorts of axis-organizing COH-3/4 complexes (averaging 3 per cohort), which are insufficient to confer cohesion but can bind to individual chromatids, suggesting a mechanism to enable formation of asymmetric sister-chromatid loops. Indeed, immunofluorescence fluorescence in situ hybridization (FISH) assays demonstrate frequent asymmetry in genomic content between the loops formed on sister chromatids. We discuss how features of chromosome axis/loop architecture inferred from our data can help to explain enigmatic, yet essential, aspects of the meiotic program.

    View details for DOI 10.1371/journal.pbio.3000817

    View details for PubMedID 32813728

  • Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells SCIENCE Bintu, B., Mateo, L. J., Su, J., Sinnott-Armstrong, N. A., Parker, M., Kinrot, S., Yamaya, K., Boettiger, A. N., Zhuang, X. 2018; 362 (6413): 419-+