CoChat
Sign Up
Cited by 3Genomics and Chromatin DynamicsMicrotubule and mitosis dynamicsNuclear Structure and Function

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Cell cycle and age-related modulations of mouse chromosome stiffness

Open access
Liu, Ning, Qiang, Wenan, Jordan, Philip W, Marko, John F, Qiao, Huanyu·2025·eLife
DOI 10.7554/elife.97403PMC PMC11996174

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a tenfold increase in stiffness (Young’s modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower than that of MI chromosomes. We examined the role of meiosis-specific cohesin complexes in regulating chromosome stiffness. Surprisingly, the stiffness of chromosomes from three meiosis-specific cohesin mutants did not significantly differ from that of wild-type chromosomes, indicating that these cohesins may not be primary determinants of chromosome stiffness. Additionally, our findings revealed an age-related increase of chromosome stiffness for MI oocytes. Since aging is associated with elevated levels of DNA damage, we investigated the impact of etoposide-induced DNA damage on chromosome stiffness and found that it led to a reduction in stiffness in MI oocytes. Overall, our study underscores the dynamic and cyclical nature of chromosome stiffness, modulated by both the cell cycle and age-related factors.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.7554/elife.97403

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 73

  1. Alberts, 2002, Chromosomal DNA and Its Packaging in the Chromatin Fiber
  2. Antonin, 2016, Chromosome condensation and decondensation during mitosis, Current Opinion in Cell Biology, 40, 15, 10.1016/j.ceb.2016.01.013 · DOI
  3. Batty, 2019, Mitotic chromosome mechanics: how cells segregate their genome, Trends in Cell Biology, 29, 717, 10.1016/j.tcb.2019.05.007 · DOI
  4. Biggs, 2019, Effects of altering histone posttranslational modifications on mitotic chromosome structure and mechanics, Molecular Biology of the Cell, 30, 820, 10.1091/mbc.E18-09-0592 · DOI
  5. Biggs, 2020, Micromanipulation of prophase I chromosomes from mouse spermatocytes reveals high stiffness and gel-like chromatin organization, Communications Biology, 3, 10.1038/s42003-020-01265-w · DOI
  6. Carofiglio, 2013, SPO11-independent DNA repair foci and their role in meiotic silencing, PLOS Genetics, 9, 10.1371/journal.pgen.1003538 · DOI
  7. Cohen-Fix, 2000, Sister chromatid separation: falling apart at the seams, Current Biology, 10, R816, 10.1016/s0960-9822(00)00799-5 · DOI
  8. De Cecco, 2011, Nuclear protein accumulation in cellular senescence and organismal aging revealed with a novel single-cell resolution fluorescence microscopy assay, Aging, 3, 955, 10.18632/aging.100372 · DOI
  9. de Vries, 2005, Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation, Genes & Development, 19, 1376, 10.1101/gad.329705 · DOI
  10. dos Santos, 2021, DNA damage alters nuclear mechanics through chromatin reorganization, Nucleic Acids Research, 49, 340, 10.1093/nar/gkaa1202 · DOI
  11. Duro, 2015, From equator to pole: splitting chromosomes in mitosis and meiosis, Genes & Development, 29, 109, 10.1101/gad.255554.114 · DOI
  12. Earnshaw, 1983, Architecture of metaphase chromosomes and chromosome scaffolds, The Journal of Cell Biology, 96, 84, 10.1083/jcb.96.1.84 · DOI
  13. Faggioli, 2011, Chromosomal aneuploidy in the aging brain, Mechanisms of Ageing and Development, 132, 429, 10.1016/j.mad.2011.04.008 · DOI
  14. Godek, 2018, Quantitative Methods to Measure Aneuploidy and Chromosomal Instability, 10.1016/bs.mcb.2018.03.002 · DOI
  15. Gordon, 2021, Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis, PLOS Genetics, 17, 10.1371/journal.pgen.1009205 · DOI
  16. Gyuricza, 2016, Dynamic and stable cohesins regulate synaptonemal complex assembly and chromosome segregation, Current Biology, 26, 1688, 10.1016/j.cub.2016.05.006 · DOI
  17. Hainsworth, 1995, Etoposide: twenty years later, Annals of Oncology, 6, 325, 10.1093/oxfordjournals.annonc.a059180 · DOI
  18. Harton, 2012, Chromosomal disorders and male infertility, Asian Journal of Andrology, 14, 32, 10.1038/aja.2011.66 · DOI
  19. He, 2018, Chromosomal instability-induced senescence potentiates cell non-autonomous tumourigenic effects, Oncogenesis, 7, 10.1038/s41389-018-0072-4 · DOI
  20. Herrán, 2011, The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility, The EMBO Journal, 30, 3091, 10.1038/emboj.2011.222 · DOI
  21. Heyting, 1996, Synaptonemal complexes: structure and function, Current Opinion in Cell Biology, 8, 389, 10.1016/s0955-0674(96)80015-9 · DOI
  22. Hochwagen, 2008, Meiosis, Current Biology, 18, R641, 10.1016/j.cub.2008.06.013 · DOI
  23. Hochwagen, 2010, Meiosis: a PRDM9 guide to the hotspots of recombination, Current Biology, 20, R271, 10.1016/j.cub.2010.01.048 · DOI
  24. Hollingsworth, 2020, A new role for the synaptonemal complex in the regulation of meiotic recombination, Genes & Development, 34, 1562, 10.1101/gad.345488.120 · DOI
  25. Hopkins, 2014, Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes, PLOS Genetics, 10, 10.1371/journal.pgen.1004413 · DOI
  26. Hornick, 2015, Age-associated alterations in the micromechanical properties of chromosomes in the mammalian egg, Journal of Assisted Reproduction and Genetics, 32, 765, 10.1007/s10815-015-0453-y · DOI
  27. Horta, 2020, Female ageing affects the DNA repair capacity of oocytes in IVF using a controlled model of sperm DNA damage in mice, Human Reproduction, 35, 529, 10.1093/humrep/dez308 · DOI
  28. Hoskins, 1994, Oral etoposide is active against platinum-resistant epithelial ovarian cancer, Journal of Clinical Oncology, 12, 60, 10.1200/JCO.1994.12.1.60 · DOI
  29. Ishiguro, 2011, A new meiosis‐specific cohesin complex implicated in the cohesin code for homologous pairing, EMBO Reports, 12, 267, 10.1038/embor.2011.2 · DOI
  30. Kleckner, 2004, A mechanical basis for chromosome function, PNAS, 101, 12592, 10.1073/pnas.0402724101 · DOI
  31. Kolano, 2012, Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension, PNAS, 109, 10.1073/pnas.1204686109 · DOI
  32. Koshland, 1996, MITOTIC CHROMOSOME CONDENSATION, Annual Review of Cell and Developmental Biology, 12, 305, 10.1146/annurev.cellbio.12.1.305 · DOI
  33. Kschonsak, 2015, Shaping mitotic chromosomes: from classical concepts to molecular mechanisms, BioEssays, 37, 755, 10.1002/bies.201500020 · DOI
  34. Laemmli UK, Cheng SM, Adolph KW, Paulson JR, Brown JA, Baumbach WR. 1978. Metaphase chromosome structure: the role of nonhistone proteins. Cold Spring Harbor Symposia on Quantitative Biology. · DOI
  35. Lee, 2003, Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis, Journal of Cell Science, 116, 2781, 10.1242/jcs.00495 · DOI
  36. Lee, 2011, Condensins I and II are essential for construction of bivalent chromosomes in mouse oocytes, Molecular Biology of the Cell, 22, 3465, 10.1091/mbc.E11-05-0423 · DOI
  37. Lister, 2010, Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of cohesin and Sgo2, Current Biology, 20, 1511, 10.1016/j.cub.2010.08.023 · DOI
  38. Ma, 2020, Why is oocyte aneuploidy increased with maternal aging?, Journal of Genetics and Genomics = Yi Chuan Xue Bao, 47, 659, 10.1016/j.jgg.2020.04.003 · DOI
  39. Maeshima, 2003, A two-step scaffolding model for mitotic chromosome assembly, Developmental Cell, 4, 467, 10.1016/s1534-5807(03)00092-3 · DOI
  40. Marangos, 2015, DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age, Nature Communications, 6, 10.1038/ncomms9706 · DOI
  41. Marcon, 2005, The evolution of meiosis: recruitment and modification of somatic DNA-repair proteins, BioEssays, 27, 795, 10.1002/bies.20264 · DOI
  42. Marko, 1997, Polymer models of meiotic and mitotic chromosomes, Molecular Biology of the Cell, 8, 2217, 10.1091/mbc.8.11.2217 · DOI
  43. McGuinness, 2005, Shugoshin prevents dissociation of cohesin from centromeres during mitosis in vertebrate cells, PLOS Biology, 3, 10.1371/journal.pbio.0030086 · DOI
  44. Menendez, 2022, Etoposide-induced DNA damage is increased in p53 mutants: identification of ATR and other genes that influence effects of p53 mutations on Top2-induced cytotoxicity, Oncotarget, 13, 332, 10.18632/oncotarget.28195 · DOI · Paper page
  45. Nakagawa, 2017, Intrinsically defective microtubule dynamics contribute to age-related chromosome segregation errors in mouse oocyte meiosis-I, Current Biology, 27, 1040, 10.1016/j.cub.2017.02.025 · DOI
  46. Oliviero, 2022, Distinct and diverse chromatin proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions, eLife, 11, 10.7554/eLife.73524 · DOI
  47. Paulson, 1977, The structure of histone-depleted metaphase chromosomes, Cell, 12, 817, 10.1016/0092-8674(77)90280-x · DOI
  48. Paulson, 2021, Mitotic chromosomes, Seminars in Cell & Developmental Biology, 117, 7, 10.1016/j.semcdb.2021.03.014 · DOI
  49. Peters, 2008, The cohesin complex and its roles in chromosome biology, Genes & Development, 22, 3089, 10.1101/gad.1724308 · DOI
  50. Poirier, 2002, Mitotic chromosomes are chromatin networks without a mechanically contiguous protein scaffold, PNAS, 99, 15393, 10.1073/pnas.232442599 · DOI
  51. Pope, 2006, Proteolysis of mitotic chromosomes induces gradual and anisotropic decondensation correlated with a reduction of elastic modulus and structural sensitivity to rarely cutting restriction enzymes, Molecular Biology of the Cell, 17, 104, 10.1091/mbc.e05-04-0321 · DOI
  52. Potapova, 2017, The consequences of chromosome segregation errors in mitosis and meiosis, Biology, 6, 1, 10.3390/biology6010012 · DOI
  53. Powers, 2016, The meiotic recombination activator PRDM9 trimethylates both H3K36 and H3K4 at recombination hotspots in vivo, PLOS Genetics, 12, 10.1371/journal.pgen.1006146 · DOI
  54. Rog, 2017, The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors, eLife, 6, 10.7554/eLife.21455 · DOI
  55. Rong, 2016, Meiotic cohesin subunits RAD21L and REC8 are positioned at distinct regions between lateral elements and transverse filaments in the synaptonemal complex of mouse spermatocytes, The Journal of Reproduction and Development, 62, 623, 10.1262/jrd.2016-127 · DOI
  56. Selesniemi, 2011, Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle defects in mice by dietary and genetic strategies, PNAS, 108, 12319, 10.1073/pnas.1018793108 · DOI
  57. Shammas, 2011, Telomeres, lifestyle, cancer, and aging, Current Opinion in Clinical Nutrition and Metabolic Care, 14, 28, 10.1097/MCO.0b013e32834121b1 · DOI
  58. Soriano-Tárraga, 2019, Epigenetics and aging, Handb, Nutr. Diet, Epigenetics, 2, 1413, 10.1007/978-3-319-55530-0_123 · DOI
  59. Strom, 2021, HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics, eLife, 10, 10.7554/eLife.63972 · DOI
  60. Sun, 2018, Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold, Chromosome Research, 26, 277, 10.1007/s10577-018-9584-1 · DOI
  61. Thakur, 1983, Covalent modifications of chromosomal proteins during aging, Archives of Gerontology and Geriatrics, 2, 1, 10.1016/0167-4943(83)90012-2 · DOI
  62. Theisen, 2010, Disorders caused by chromosome abnormalities, The Application of Clinical Genetics, 3, 159, 10.2147/TACG.S8884 · DOI
  63. Thompson, 2011, Chromosomes and cancer cells, Chromosome Research, 19, 433, 10.1007/s10577-010-9179-y · DOI
  64. Tian, 2021, Age-cumulative effect of REC8 reduction on meiotic chromosome segregation errors in mice, Reproductive and Developmental Medicine, 5, 193, 10.4103/2096-2924.327880 · DOI
  65. Tsutsumi, 2014, Age-related decrease of meiotic cohesins in human oocytes, PLOS ONE, 9, 10.1371/journal.pone.0096710 · DOI
  66. Vagnarelli, 2013, Chromatin Reorganization through Mitosis, 10.1016/B978-0-12-410523-2.00006-7 · DOI
  67. Wang, 2017, The histone codes for meiosis, Reproduction, 154, R65, 10.1530/REP-17-0153 · DOI
  68. Wang, 2022, Epigenetic regulation of aging: implications for interventions of aging and diseases, Signal Transduction and Targeted Therapy, 7, 10.1038/s41392-022-01211-8 · DOI
  69. Ward, 2016, Genetic interactions between the meiosis-specific cohesin components, STAG3, REC8, and RAD21L, G3: Genes, Genomes, Genetics, 6, 1713, 10.1534/g3.116.029462 · DOI
  70. Wood, 1990, Mitotic chromatin condensation in vitro using somatic cell extracts and nuclei with variable levels of endogenous topoisomerase II, The Journal of Cell Biology, 111, 2839, 10.1083/jcb.111.6.2839 · DOI
  71. Xu, 2005, Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis, Developmental Cell, 8, 949, 10.1016/j.devcel.2005.03.018 · DOI
  72. Zheng, 2019, The role of 3D genome organization in development and cell differentiation, Nature Reviews. Molecular Cell Biology, 20, 535, 10.1038/s41580-019-0132-4 · DOI
  73. Zickler, 2023, Meiosis: dances between homologs, Annual Review of Genetics, 57, 1, 10.1146/annurev-genet-061323-044915 · DOI

Metadata

Authors
Liu, N., Qiang, W., Jordan, P. W., Marko, J. F., & Qiao, H.
Affiliations
  • University of Illinois Urbana-Champaign (US)
  • Northwestern University (US)
  • Johns Hopkins University (US)
Corresponding author
  • Marko, John F
  • Qiao, Huanyu
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2025-04-14
Volume
13
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.97403
PMC
PMC11996174
OpenAlex
W4396720040
Cited by
3
References
1
Citations by year
2026: 3
Type
posted content
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health (R00 HD082375, R01 GM135549, UM1 HG011536, R01 GM105847, R01 GM117155, T32 ES007326, U54 CA203000)
Topics
  • 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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
Young's modulus, meiosis, metaphase I oocytes, metaphase II oocytes, aging, DNA damage, etoposide, cell cycle, chromosome structure, mouse oocytes
MeSH terms
Cohesins, Aging, Animals, Cell Cycle, Chromosomal Proteins, Non-Histone, Chromosomes, DNA Damage, Female, Meiosis, Metaphase, Oocytes, Cell Cycle Proteins, Chromosomes, Mammalian, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review