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Homologue engagement controls meiotic DNA break number and distribution

Abstract

Meiotic recombination promotes genetic diversification as well as pairing and segregation of homologous chromosomes, but the double-strand breaks (DSBs) that initiate recombination are dangerous lesions that can cause mutation or meiotic failure. How cells control DSBs to balance between beneficial and deleterious outcomes is not well understood. Here we test the hypothesis that DSB control involves a network of intersecting negative regulatory circuits. Using multiple complementary methods, we show that DSBs form in greater numbers in Saccharomyces cerevisiae cells lacking ZMM proteins, a suite of recombination-promoting factors traditionally regarded as acting strictly downstream of DSB formation. ZMM-dependent DSB control is genetically distinct from a pathway tying break formation to meiotic progression through the Ndt80 transcription factor. These counterintuitive findings suggest that homologous chromosomes that have successfully engaged one another stop making breaks. Genome-wide DSB maps uncover distinct responses by different subchromosomal domains to the ZMM mutation zip3 (also known as cst9), and show that Zip3 is required for the previously unexplained tendency of DSB density to vary with chromosome size. Thus, feedback tied to ZMM function contributes in unexpected ways to spatial patterning of recombination.

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Figure 1: More DSBs form in ZMM mutants.
Figure 2: Hyper-rec phenotype of ZMM mutants.
Figure 3: Separable effects of ndt80 and ZMM mutations.
Figure 4: Altered DSB distribution in zip3 mutants.

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Sequencing data were deposited at GEO under accession number GSE48299.

References

  1. Keeney, S. Mechanism and control of meiotic recombination initiation. Curr. Top. Dev. Biol. 52, 1–53 (2001)

    Article  CAS  PubMed  Google Scholar 

  2. Lange, J. et al. ATM controls meiotic double-strand-break formation. Nature 479, 237–240 (2011)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  3. Joyce, E. F. et al. Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair. J. Cell Biol. 195, 359–367 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhang, L., Kim, K. P., Kleckner, N. E. & Storlazzi, A. Meiotic double-strand breaks occur once per pair of (sister) chromatids and, via Mec1/ATR and Tel1/ATM, once per quartet of chromatids. Proc. Natl Acad. Sci. USA 108, 20036–20041 (2011)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  5. Carballo, J. A. et al. Budding yeast ATM/ATR control meiotic double-strand break (DSB) levels by down-regulating Rec114, an essential component of the DSB-machinery. PLoS Genet. 9, e1003545 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bhagat, R., Manheim, E. A., Sherizen, D. E. & McKim, K. S. Studies on crossover-specific mutants and the distribution of crossing over in Drosophila females. Cytogenet. Genome Res. 107, 160–171 (2004)

    Article  CAS  PubMed  Google Scholar 

  7. Henzel, J. V. et al. An asymmetric chromosome pair undergoes synaptic adjustment and crossover redistribution during Caenorhabditis elegans meiosis: implications for sex chromosome evolution. Genetics 187, 685–699 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kauppi, L. et al. Numerical constraints and feedback control of double-strand breaks in mouse meiosis. Genes Dev. 27, 873–886 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lynn, A., Soucek, R. & Borner, G. V. ZMM proteins during meiosis: crossover artists at work. Chromosome Res. 15, 591–605 (2007)

    Article  CAS  PubMed  Google Scholar 

  10. Neale, M. J., Pan, J. & Keeney, S. Endonucleolytic processing of covalent protein-linked DNA double-strand breaks. Nature 436, 1053–1057 (2005)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pan, J. et al. A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation. Cell 144, 719–731 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xu, L., Ajimura, M., Padmore, R., Klein, C. & Kleckner, N. NDT80, a meiosis-specific gene required for exit from pachytene in Saccharomyces cerevisiae. Mol. Cell. Biol. 15, 6572–6581 (1995)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sym, M., Engebrecht, J. A. & Roeder, G. S. ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis. Cell 72, 365–378 (1993)

    Article  CAS  PubMed  Google Scholar 

  14. Ross-Macdonald, P. & Roeder, G. S. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Cell 79, 1069–1080 (1994)

    Article  CAS  PubMed  Google Scholar 

  15. Hollingsworth, N. M., Ponte, L. & Halsey, C. MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes Dev. 9, 1728–1739 (1995)

    Article  CAS  PubMed  Google Scholar 

  16. Chua, P. R. & Roeder, G. S. Zip2, a meiosis-specific protein required for the initiation of chromosome synapsis. Cell 93, 349–359 (1998)

    Article  CAS  PubMed  Google Scholar 

  17. Agarwal, S. & Roeder, G. S. Zip3 provides a link between recombination enzymes and synaptonemal complex proteins. Cell 102, 245–255 (2000)

    Article  CAS  PubMed  Google Scholar 

  18. Tsubouchi, T., Zhao, H. & Roeder, G. S. The meiosis-specific zip4 protein regulates crossover distribution by promoting synaptonemal complex formation together with zip2. Dev. Cell 10, 809–819 (2006)

    Article  CAS  PubMed  Google Scholar 

  19. Shinohara, M., Oh, S. D., Hunter, N. & Shinohara, A. Crossover assurance and crossover interference are distinctly regulated by the ZMM proteins during yeast meiosis. Nature Genet. 40, 299–309 (2008)

    Article  CAS  PubMed  Google Scholar 

  20. Börner, G. V., Kleckner, N. & Hunter, N. Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117, 29–45 (2004)

    Article  PubMed  Google Scholar 

  21. Allers, T. & Lichten, M. Differential timing and control of noncrossover and crossover recombination during meiosis. Cell 106, 47–57 (2001)

    Article  CAS  PubMed  Google Scholar 

  22. Gray, S., Allison, R. M., Garcia, V., Goldman, A. S. & Neale, M. J. Positive regulation of meiotic DNA double-strand break formation by activation of the DNA damage checkpoint kinase Mec1(ATR). Open Biol. 3, 130019 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Rockmill, B. et al. High throughput sequencing reveals alterations in the recombination signatures with diminishing Spo11 activity. PLoS Genet. 9, e1003932 (2013)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Tung, K. S., Hong, E. J. & Roeder, G. S. The pachytene checkpoint prevents accumulation and phosphorylation of the meiosis-specific transcription factor Ndt80. Proc. Natl Acad. Sci. USA 97, 12187–12192 (2000)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  25. Rosu, S. et al. The C. elegans DSB-2 protein reveals a regulatory network that controls competence for meiotic DSB formation and promotes crossover assurance. PLoS Genet. 9, e1003674 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Stamper, E. L. et al. Identification of DSB-1, a protein required for initiation of meiotic recombination in Caenorhabditis elegans, illuminates a crossover assurance checkpoint. PLoS Genet. 9, e1003679 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wojtasz, L. et al. Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. PLoS Genet. 5, e1000702 (2009)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Smith, A. V. & Roeder, G. S. The yeast Red1 protein localizes to the cores of meiotic chromosomes. J. Cell Biol. 136, 957–967 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kee, K., Protacio, R. U., Arora, C. & Keeney, S. Spatial organization and dynamics of the association of Rec102 and Rec104 with meiotic chromosomes. EMBO J. 23, 1815–1824 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chen, S. Y. et al. Global analysis of the meiotic crossover landscape. Dev. Cell 15, 401–415 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nakagawa, T. & Ogawa, H. The Saccharomyces cerevisiae MER3 gene, encoding a novel helicase-like protein, is required for crossover control in meiosis. EMBO J. 18, 5714–5723 (1999)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jessop, L., Rockmill, B., Roeder, G. S. & Lichten, M. Meiotic chromosome synapsis-promoting proteins antagonize the anti-crossover activity of sgs1. PLoS Genet. 2, e155 (2006)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Falk, J. E., Chan, A. C., Hoffmann, E. & Hochwagen, A. A. Mec1- and PP4-dependent checkpoint couples centromere pairing to meiotic recombination. Dev. Cell 19, 599–611 (2010)

    Article  CAS  PubMed  Google Scholar 

  34. Lichten, M. in Recombination and Meiosis: Models, Means, and Evolution Vol. 3 (eds R. Egel & D. H. Lankenau ) 165–193 (Springer-Verlag, 2008)

    Book  Google Scholar 

  35. Kaback, D. B., Guacci, V., Barber, D. & Mahon, J. W. Chromosome size-dependent control of meiotic recombination. Science 256, 228–232 (1992)

    Article  ADS  CAS  PubMed  Google Scholar 

  36. Blitzblau, H. G., Bell, G. W., Rodriguez, J., Bell, S. P. & Hochwagen, A. Mapping of meiotic single-stranded DNA reveals double-stranded-break hotspots near centromeres and telomeres. Curr. Biol. 17, 2003–2012 (2007)

    Article  CAS  PubMed  Google Scholar 

  37. Buhler, C., Borde, V. & Lichten, M. Mapping meiotic single-strand DNA reveals a new landscape of DNA double-strand breaks in Saccharomyces cerevisiae. PLoS Biol. 5, e324 (2007)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Panizza, S. et al. Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination. Cell 146, 372–383 (2011)

    Article  CAS  PubMed  Google Scholar 

  39. Serrentino, M. E., Chaplais, E., Sommermeyer, V. & Borde, V. Differential association of the conserved SUMO ligase Zip3 with meiotic double-strand break sites reveals regional variations in the outcome of meiotic recombination. PLoS Genet. 9, e1003416 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Borde, V. & de Massy, B. Programmed induction of DNA double strand breaks during meiosis: setting up communication between DNA and the chromosome structure. Curr. Opin. Genet. Dev. 23, 147–155 (2013)

    Article  CAS  PubMed  Google Scholar 

  41. Pineda-Krch, M. & Redfield, R. J. Persistence and loss of meiotic recombination hotspots. Genetics 169, 2319–2333 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Thacker, D. Meiotic Recombination in Saccharomyces Cerevisiae: from New Assays to New Insights. PhD thesis, Cornell Univ. (2012)

  43. Alani, E., Padmore, R. & Kleckner, N. Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination. Cell 61, 419–436 (1990)

    Article  CAS  PubMed  Google Scholar 

  44. Padmore, R., Cao, L. & Kleckner, N. Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae. Cell 66, 1239–1256 (1991)

    Article  CAS  PubMed  Google Scholar 

  45. Borde, V., Goldman, A. S. & Lichten, M. Direct coupling between meiotic DNA replication and recombination initiation. Science 290, 806–809 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Diaz, R. L., Alcid, A. D., Berger, J. M. & Keeney, S. Identification of residues in yeast Spo11p critical for meiotic DNA double-strand break formation. Mol. Cell. Biol. 22, 1106–1115 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Murakami, H., Borde, V., Nicolas, A. & Keeney, S. Gel electrophoresis assays for analyzing DNA double-strand breaks in Saccharomyces cerevisiae at various spatial resolutions. Methods Mol. Biol. 557, 117–142 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Neale, M. J. & Keeney, S. End-labeling and analysis of Spo11-oligonucleotide complexes in Saccharomyces cerevisiae. Methods Mol. Biol. 557, 183–195 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. R Development Core Team. R: A language and environment for statistical computing. (R Foundation for Statistical Computing, Vienna, Austria, 2012)

  50. Rumble, S. M. et al. SHRiMP: accurate mapping of short color-space reads. PLOS Comput. Biol. 5, e1000386 (2009)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Abdullah, M. F. & Borts, R. H. Meiotic recombination frequencies are affected by nutritional states in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 98, 14524–14529 (2001)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  52. Cotton, V. E., Hoffmann, E. R., Abdullah, M. F. & Borts, R. H. Interaction of genetic and environmental factors in Saccharomyces cerevisiae meiosis: the devil is in the details. Methods Mol. Biol. 557, 3–20 (2009)

    Article  CAS  PubMed  Google Scholar 

  53. Martini, E., Diaz, R. L., Hunter, N. & Keeney, S. Crossover homeostasis in yeast meiosis. Cell 126, 285–295 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Vader, G. et al. Protection of repetitive DNA borders from self-induced meiotic instability. Nature 477, 115–119 (2011)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to S. Burgess, N. Hunter, N. Kleckner, K. Ohta, M. Rout and A. Shinohara for strains or epitope tagging constructs; F. Klein for sharing data; S. Shuman for gifts of T4 RNA ligase; A. Viale and the Memorial Sloan Kettering Cancer Center (MSKCC) Genomics Core Laboratory for sequencing; and N. Socci and the MSKCC Bioinformatics Core for assistance mapping Spo11 oligos. This work was supported by National Institutes of Health grant R01 GM058673. S.K. is an Investigator of the Howard Hughes Medical Institute.

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Authors

Contributions

D.T., N.M. and X.Z. performed experiments and analysed the data. N.M. optimized purification of the Spo11–protein A fusion, prepared the sequencing libraries to map DSBs and performed preliminary data analysis on sequencing reads. S.K. analysed sequencing data. D.T. and S.K. wrote the paper.

Corresponding author

Correspondence to Scott Keeney.

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The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Chromosomal breaks in msh5 and zip1 mutants.

Representative pulsed-field gel Southern blots probed for chromosome IX are shown, labelled as in Fig. 1b.

Extended Data Figure 2 DSB formation appears normal in SPO11-Flag and SPO11-PrA strains.

a, Southern blots probed for chromosome III. High molecular weight chromosomal DNA was purified 6 h after transfer to sporulation medium from meiotic rad50S cultures carrying the indicated SPO11 alleles (in spo11-yf the catalytic tyrosine 135 is mutated to phenylalanine), then separated on pulsed-field electrophoresis gels. Samples from a rad50S spo11-HA strain are shown for comparison; haemagglutinin-tagged Spo11 has reduced DSB frequency. Each lane represents an independent culture (SPO11+ samples from the same cultures were run on both gels). PrA, protein A. b, Quantification of blots in panel a and separate blots (not shown) probed for chromosomes VII or VIII. Break frequencies are per cent of DNA in lane (mean ± s.d. of 3–4 cultures). Numbers in parentheses indicate values from each tagged strain relative to SPO11+ for the same chromosome. Relative DSB frequencies at the bottom are averages across the three chromosomes assayed.

Extended Data Figure 3 Spo11–oligo complexes in msh5 and zip1 mutants.

Representative time courses are shown.

Extended Data Figure 4 Analysis of recombination at three natural DSB hotspots.

a, b, Recombination reporters at the ERG1 (a) and GAT1 (b) hotspots. ce, Representative Southern blots of parental and recombinant DNA molecules at CCT6 (c), ERG1 (d) and GAT1 (e). The arrowhead in e indicates a non-reproducible radiolabelled species. f, Local distribution of DSBs around recombination reporter locations is not altered in zip3 mutants. Spo11-oligo profiles (averages for wild type and zip3 mutant) are smoothed with 201-bp Hann window; zip3 values are offset to separate profiles.

Extended Data Figure 5 Direct analysis of DSB formation at natural hotspots.

ad, Representative Southern blots of DNA separated on a conventional agarose gel and probed for GAT1 (a), CCT6 (b, c) and ERG1 (d). The arrowhead in a indicates signal from the CCT6 parental band that remained after stripping and reprobing for GAT1. e, Quantifications for bd (mean ± s.d. for 3 cultures).

Extended Data Figure 6 Spo11–oligo complexes in msh5 ndt80 double mutant.

Representative time courses are shown.

Extended Data Figure 7 Effects of dmc1 deletion or spo11 hypomorphic mutation on ZMM mutant phenotypes.

a, b, ZMM status is irrelevant in a dmc1 background. Broken chromosomes accumulate to similar levels in a dmc1 single mutant and dmc1 zmm double mutants. Representative pulsed-field gel Southern blots probed for chromosome IX are in a and Poisson-corrected quantification of DSBs is in b (mean ± s.d., 3 cultures). c, Reducing Spo11 activity in a zip3 mutant partially alleviates the prophase I delay/arrest. Meiotic progression was assessed by staining with DAPI (4′,6-diamidino-2-phenylindole) and measuring the percentage of cells that had completed meiosis I (MI) with or without completing meiosis II ( ± MII). Data are means ± s.d. for 3 cultures, except wild type and spo11-HA, each analysed once.

Extended Data Figure 8 Spo11-oligo mapping in wild type and zip3 mutant.

a, b, Quantitative reproducibility of Spo11-oligo maps. In a, comparisons are shown for individual wild type (WT) or zip3 data sets from the present study, or the previously published spo11-HA data (from ref. 11). Uniquely mapped Spo11 oligos were summed in non-overlapping 5-kb bins and expressed as RPM per kb (plotted on a log scale). In b, pairwise correlation coefficients for the data sets from the current study are shown (Pearson’s r; box colours scaled from blue to red proportional to strength of correlation). For the comparison of this study’s wild-type average with data from Pan et al., r = 0.949. Note that Pan et al. used a different strain background with different auxotrophies, which may alter DSB distributions51,52, and a hypomorphic spo11 allele (spo11-HA), which may affect DSBs to different extents at different locations53. Note that biological replicates (WT-1 versus WT-2 or zip3-1 versus zip3-2) agreed better than comparisons between cultures of different genotype. c, DSBs form at the same hotspots and with similar distribution within and between hotspots in wild type and zip3. Unsmoothed Spo11-oligo maps are shown in the vicinity of the well-characterized ARE1 (YCR048w) hotspot.

Extended Data Figure 9 Changes in the DSB landscape in zip3 mutant.

a, Change in Spo11-oligo counts in hotspots grouped by chromosomal context. Tel, within 20 kb of telomeres; Cen, within ± 10 kb of centromeres; rDNA, from 60 kb leftward to 30 kb rightward of rDNA; Interstitial, all others. Dashed lines mark values assumed as no change and average change (1.8-fold). Boxes indicate median and interquartile range; whiskers indicate the most extreme data points which are ≤1.5 times the interquartile range from the box; individual points are outliers. Subtelomeric and pericentric zones show less increase in zip3 on average, thus, ZMM-dependent feedback contributes less than other, unknown factors to suppressing DSBs in these regions. The zone near the rDNA showed no increase or was even decreased; thus, zip3 mutants are competent for this region’s DSB suppression, which is dependent on the ATPase Pch2 and the replication factor Orc1 (ref. 54). Note that the remaining interstitial hotspots showed highly variable response to zip3 mutation (>20 fold). b, Correlation between log-fold change in Spo11-oligo counts in zip3 and the binding of the indicated proteins, binned in non-overlapping windows of varying size. Closed symbols, P < 0.05. ChIP data are from ref. 38. c, Average ChIP profiles around interstitial hotspots divided into three equal-sized groups according to the average fold change in zip3. Top, the box and whisker plot (as described for a) shows the distribution of fold changes for the three groups. Bottom, ChIP profiles for each of the indicated proteins. Note that the profiles lie atop one another for Rec102 and Rec104. Dashed arrows indicate direction of the change in the average profiles with increasing fold change in zip3. ChIP data are from refs 38 and 39. d, High degree of colinearity of log2-transformed ChIP data38 for Rec114, Mei4 and Mer2 (which are essential for DSB formation) and Hop1 and Red1 (axis proteins that promote normal DSB formation). More than 90% of the variance for this combination of ChIP data is captured in the first principal component (PC1). The high degree of correlation between these proteins was described previously38. e, Correlations between the fold change in zip3 (zip3 FC, log2 and assuming 1.8-fold increase genome-wide) and various chromosomal features: principal component 1 for Rec114, Mei4, Mer2, Hop1 and Red1 ChIP data (same as in d); chromosome size (loge(bp)); G+C content (%); and ChIP data for the indicated proteins (log2). In d and e, top right panels show pairwise scatter plots and bottom left panels show corresponding correlation coefficients (Pearson’s r) for data for interstitial regions binned in 35-kb non-overlapping windows. Essentially identical results were obtained with different window sizes (20–40 kb) or with varying placement of windows (data not shown). f, Essentially no correlation between DSB activity in wild type and change in zip3, whether considering interstitial regions divided into non-overlapping 35-kb bins (upper panel) or interstitial hotspots (lower panel). A 1.8-fold increase genome-wide in zip3 is assumed. Note: fold change is labelled according to a linear scale but plotted in a log scale in panels a, c, f.

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Thacker, D., Mohibullah, N., Zhu, X. et al. Homologue engagement controls meiotic DNA break number and distribution. Nature 510, 241–246 (2014). https://doi.org/10.1038/nature13120

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