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PreprintCited by 29DNA Repair MechanismsGenomics and Chromatin DynamicsMicrotubule and mitosis dynamics

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Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

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Milano, Carolyn R., Ur, Sarah N., Gu, Yajie, Tromer, Eelco C., Zhang, Jessie, Hochwagen, Andreas, Corbett, Kevin D.·2023·The EMBO Journal
DOI 10.1101/2023.03.04.531117PMC PMC10907721

Preprint — published as 10.1038/s44318-024-00034-3 · Paper page

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Abstract

The meiotic chromosome axis coordinates chromosome organization and interhomolog recombination in meiotic prophase and is essential for fertility. In S. cerevisiae , the HORMAD protein Hop1 mediates enrichment of axis proteins at nucleosome-rich genomic islands through a central chromatin-binding region (CBR). Here, we use cryoelectron microscopy to show that the Hop1 CBR directly recognizes bent nucleosomal DNA through a composite interface in its PHD and winged helix-turn-helix domains. Targeted disruption of the Hop1 CBR-nucleosome interface causes loss of axis proteins from nucleosome-rich islands, reduces meiotic DNA double-strand breaks (DSBs), and leads to defects in chromosome synapsis. Synthetic effects with the disassemblase Pch2 suggest that nucleosome binding delays a conformational switch in Hop1 from a DSB-promoting, Pch2-inaccessible state to a DSB-inactive, Pch2-accessible state to regulate the extent of meiotic DSB formation. Phylogenetic analyses of meiotic HORMADs reveal an ancient origin of this domain, suggesting that these mechanisms are broadly conserved.

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  1. 10.1038/35066065 · DOI
  2. 10.1093/hmg/ddm243 · DOI
  3. 2022, Chromosome architecture and homologous recombination in meiosis, Front Cell Dev Biol, 10, 1097446
  4. 10.1146/annurev-genet-071719-020235 · DOI
  5. 10.1101/cshperspect.a016626 · DOI
  6. 10.3390/genes13020200 · DOI
  7. 10.7554/eLife.40372 · DOI
  8. 10.1083/jcb.201509076 · DOI
  9. 10.3390/genes13050777 · DOI
  10. 2019, Organization of Chromosomal DNA by SMC Complexes, Annu. Rev. Genet, 53, 445, 10.1146/annurev-genet-112618-043633 · DOI
  11. 10.1038/nsmb.3208 · DOI
  12. 10.1101/gad.349286.121 · DOI
  13. 10.1016/S0092-8674(00)80609-1 · DOI
  14. 10.1016/0092-8674(90)90216-2 · DOI
  15. 10.1016/j.cell.2011.07.003 · DOI
  16. 2000, Meiotic segregation, synapsis, and recombination checkpoint functions require physical interaction between the chromosomal proteins Red1p and Hop1p. Mol, Cell. Biol, 20, 6646
  17. 10.1016/j.cell.2008.01.035 · DOI
  18. 10.1091/mbc.E05-05-0465 · DOI
  19. 2007, Mek1 kinase is regulated to suppress double-strand break repair between sister chromatids during budding yeast meiosis. Mol, Cell. Biol, 27, 5456
  20. 10.1073/pnas.0711864105 · DOI
  21. 10.1016/S0092-8674(00)80741-2 · DOI
  22. 10.1073/pnas.1310755111 · DOI
  23. 10.1371/journal.pbio.1002369 · DOI
  24. 10.1371/journal.pgen.1000702 · DOI
  25. 10.1101/gad.342873.120 · DOI
  26. 10.1016/j.molcel.2019.03.023 · DOI
  27. 2020, Ensuring meiotic DNA break formation in the mouse pseudoautosomal region, Nature, 582, 426, 10.1038/s41586-020-2327-4 · DOI
  28. 10.1016/j.molcel.2019.03.022 · DOI
  29. 10.1126/science.1566070 · DOI
  30. 10.1016/j.devcel.2008.07.006 · DOI
  31. 10.1038/ng0596-20 · DOI
  32. 10.1038/nature07135 · DOI
  33. 10.1038/s41586-020-2248-2 · DOI
  34. 10.1016/j.cell.2011.02.009 · DOI
  35. 10.1016/j.cub.2007.10.066 · DOI
  36. 10.7554/eLife.07424 · DOI
  37. 10.1007/s00294-021-01160-9 · DOI
  38. 10.1093/nar/gkac227 · DOI
  39. 10.1016/j.tibs.2011.03.005 · DOI
  40. 10.1038/38444 · DOI · Paper page
  41. 10.1006/jmbi.1997.1494 · DOI
  42. 10.1186/s12864-018-5368-4 · DOI
  43. 10.1016/0092-8674(90)90524-I · DOI
  44. 10.1016/0092-8674(94)90172-4 · DOI
  45. 10.1016/S0092-8674(01)00430-5 · DOI
  46. 10.1016/j.cub.2006.10.069 · DOI
  47. 10.1371/journal.pgen.1003194 · DOI
  48. 10.1038/nature13993 · DOI
  49. 10.1101/gr.213587.116 · DOI
  50. 10.1073/pnas.1821945116 · DOI
  51. 10.15252/embr.201744102 · DOI
  52. 10.1098/rsob.210049 · DOI
  53. 10.1093/NAR/GKAB1061 · DOI · Paper page
  54. 10.1534/genetics.120.303060 · DOI
  55. 10.1093/nar/gkac1160 · DOI
  56. 2018, Conformational dynamics of the Hop1 HORMA domain reveal a common mechanism with the spindle checkpoint protein Mad2, Nucleic Acids Res, 46, 279, 10.1093/nar/gkx1196 · DOI
  57. 10.1371/journal.pone.0134297 · DOI
  58. 10.7554/eLife.57720 · DOI
  59. 10.1016/S0076-6879(99)04003-3 · DOI
  60. 10.1107/S0907444909047337 · DOI · Paper page
  61. 10.1107/S0907444910045749 · DOI · Paper page
  62. 10.1107/S0021889804018047 · DOI
  63. 10.1107/S2059798319011471 · DOI · Paper page
  64. 10.1107/S0907444910007493 · DOI · Paper page
  65. 10.1107/S0907444912001308 · DOI · Paper page
  66. 10.1002/PRO.3943 · DOI
  67. 10.1038/nprot.2009.2 · DOI
  68. 10.1016/j.jmb.2010.08.039 · DOI
  69. 2021, DeepEMhancer: a deep learning solution for cryo-EM volume post-processing, Commun Biol, 4, 874, 10.1038/s42003-021-02399-1 · DOI
  70. 10.1038/nmeth.2089 · DOI · Paper page
  71. 10.1002/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO;2-U · DOI
  72. 10.1093/nar/gkt135 · DOI · Paper page
  73. 10.1038/ng.3847 · DOI
  74. 10.1371/journal.pcbi.1002195 · DOI · Paper page
  75. 10.1093/molbev/mst010 · DOI · Paper page
  76. 2022, ColabFold: making protein folding accessible to all, Nat. Methods, 19, 679, 10.1038/s41592-022-01488-1 · DOI · Paper page
  77. 10.1038/nature13120 · DOI
  78. 10.1016/j.celrep.2016.09.056 · DOI
  79. 10.1093/nar/gkw408 · DOI · Paper page
  80. 10.1002/pro.3280 · DOI

Metadata

Authors
Milano, C. R., Ur, S. N., Gu, Y., Tromer, E. C., Zhang, J., Hochwagen, A., & Corbett, K. D.
Affiliations
  • New York University (US)
  • University of California San Diego (US)
  • University of Groningen (NL)
Corresponding author
  • Hochwagen, Andreas
  • Corbett, Kevin D.
ORCID
Venue
The EMBO Journal
Publisher
openRxiv
Published
2023-03-05
Volume
43
Issue
5
Pages
836-867
ISSN
0261-4189 (ISSN-L)
DOI
10.1101/2023.03.04.531117
PMC
PMC10907721
OpenAlex
W4391654351
Cited by
29
References
1
Citations by year
2026: 14 · 2025: 5 · 2024: 9
FWCI
3.81
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • The EMBO Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders
  • National Science Foundation (T32 GM008326, P30 GM124169)
  • U.S. Department of Energy (S10OD018483, GM124169)
  • Wellcome Trust (225852/Z/22/Z, 200843/Z/16/Z)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (202.223, VI.Veni.202.223)
  • National Institutes of Health (1s10od018483-01, NIH T32, GM124169)
  • University of California, San Diego
  • National Institute of General Medical Sciences (GM139386, GM148223, F32GM139386, GM124169, GM008326, GM144121, R01GM111715, GM111715, T32GM008326, P30GM124169, R35GM144121, R35GM148223)
  • Basic Energy Sciences (S10OD018483)
  • Biological and Environmental Research (S10OD018483)
  • Lawrence Berkeley National Laboratory (S10OD018483)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
Hop1, meiotic chromosome axis, chromatin binding, nucleosome, DNA double-strand breaks, chromosome pairing, Pch2, PHD domain, Saccharomyces cerevisiae, protein-DNA interface
MeSH terms
DNA, Meiosis, Nuclear Proteins, Nucleosomes, Phylogeny, Saccharomyces cerevisiae, Cryoelectron Microscopy, Saccharomyces cerevisiae Proteins

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