CoChat
Sign Up
Cited by 162Telomeres, Telomerase, and SenescenceMicrotubule and mitosis dynamicsSperm and Testicular Function

Telomere Dysfunction Triggers Developmentally Regulated Germ Cell Apoptosis

Open access
Hemann, Michael T., Rudolph, Karl Lenhard, Strong, Margaret A., DePinho, Ronald A., Chin, Lynda, Greider, Carol W.·2001·Molecular Biology of the Cell
DOI 10.1091/mbc.12.7.2023PMC PMC55650
Open this paper in CoChat — free account

Abstract

Telomere dysfunction results in fertility defects in a number of organisms. Although data from fission yeast and Caenorhabditis elegans suggests that telomere dysfunction manifests itself primarily as defects in proper meiotic chromosome segregation, it is unclear how mammalian telomere dysfunction results in germ cell death. To investigate the specific effects of telomere dysfunction on mammalian germ cell development, we examined the meiotic progression and germ cell apoptosis in late generation telomerase null mice. Our results indicate that chromosome asynapsis and missegregation are not the cause of infertility in mice with shortened telomeres. Rather, telomere dysfunction is recognized at the onset of meiosis, and cells with telomeric defects are removed from the germ cell precursor pool. This germ cell telomere surveillance may be an important mechanism to protect against the transmission of dysfunctional telomeres and chromosomal abnormalities.

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 · 10.1091/mbc.12.7.2023

Cites

Statistics

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

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The breeding strategy produced same-strain dystrophic mice lacking telomerase, which is critical because telomere length differs among mouse strains.

    “This strategy yields same strain dystrophic mice that lack telomerase, which is critical, as telomere length differs among mouse strains (Hemann et al., 2001).”

    From Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice (2010) · cites this paper as Hemann et al., 2001

  • Signalling from short telomeres activates checkpoints that cause either senescence or apoptosis, and sometimes both at once.

    “The consequent signalling cascades activate checkpoints that induce either cellular senescence or apoptosis, and in at least some contexts both processes occur simultaneously82,85,91,95.”

    From The telomere syndromes (2012) · cites this paper as [95]

Self-check

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

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

The citation lists haven’t been fetched yet

References 42 · Cited by 162

Research works printed but not linked: 36

  1. Ahmed S, Hodgkin J. MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans. Nature. 2000;403:159–164. doi: 10.1038/35003120. [DOI] [PubMed] [Google Scholar] · DOI
  2. Allan DJ, Harmon BV, Kerr JFR. Cell death in spermatogenesis. In: Potten CS, editor. Perspectives on Mammalian Cell Death. London: Oxford University Press; 1987. pp. 229–258. [Google Scholar]
  3. Bailey SM, Meyne J, Chen DJ, Kurimasa A, Li GC, Lehnert BE, Goodwin EH. DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes. Proc Natl Acad Sci USA. 1999;96:14899–14904. doi: 10.1073/pnas.96.26.14899. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  4. Bellve AR. The molecular biology of mammalian spermatogenesis. In: Finn C A, editor. Oxford Reviews of Reproductive Biology. Oxford: Oxford University Press; 1979. pp. 159–261. [Google Scholar]
  5. Cooper JP, Watanabe Y, Nurse P. Fission yeast Taz1 protein is required for meiotic telomere clustering and recombination. Nature. 1998;392:828–831. doi: 10.1038/33947. [DOI] [PubMed] [Google Scholar] · DOI
  6. Critchlow SE, Jackson SP. DNA end-joining: from yeast to man. Trends Biochem Sci. 1998;23:394–398. doi: 10.1016/s0968-0004(98)01284-5. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  7. Dernburg AF, Sedat JW, Cande WZ, Bass HW. Cytology of telomeres. In: Blackburn EH, Greider CW, editors. Telomeres. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1995. pp. 295–338. [Google Scholar]
  8. Edelmann W, Cohen PE, Kneitz B, Winand N, Lia M, Heyer J, Kolodner R, Pollard JW, Kucherlapati R. Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nat Genet. 1999;21:123–127. doi: 10.1038/5075. [DOI] [PubMed] [Google Scholar] · DOI
  9. Enders GC, May JJ. Developmentally regulated expression of a mouse germ cell nuclear antigen examined from embryonic day 11 to adult in male and female mice. Dev Biol. 1994;163:331–340. doi: 10.1006/dbio.1994.1152. [DOI] [PubMed] [Google Scholar] · DOI
  10. Evans EP, Breckon G, Ford CE. An air-drying method for meiotic preparations from mammalian testis. Cytogenetics. 1964;3:289–294. doi: 10.1159/000129818. [DOI] [PubMed] [Google Scholar] · DOI
  11. Gao Y, Sun Y, Frank KM, Dikkes P, Fujiwara Y, Seidl KJ, Sekiguchi JM, Rathbun GA, Swat W, Wang J, Bronson RT, Malynn BA, Bryans M, Zhu C, Chaudhuri J, Davidson L, Ferrini R, Stamato T, Orkin SH, Greenberg ME, Alt FW. A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell. 1998;95:891–902. doi: 10.1016/s0092-8674(00)81714-6. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  12. Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C. Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis. Nat Genet. 1999;23:194–198. doi: 10.1038/13821. [DOI] [PubMed] [Google Scholar] · DOI
  13. Greider CW. Telomere length regulation. Annu Rev Biochem. 1996;65:337–365. doi: 10.1146/annurev.bi.65.070196.002005. [DOI] [PubMed] [Google Scholar] · DOI
  14. Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985;43:405–413. doi: 10.1016/0092-8674(85)90170-9. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  15. Herrera E, Samper E, Blasco MA. Telomere shortening in mTR−/− embryos is associated with failure to close the neural tube. EMBO J. 1999;18:1172–1181. doi: 10.1093/emboj/18.5.1172. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  16. Hsu HL, Gilley D, Blackburn EH, Chen DJ. Ku is associated with the telomere in mammals. Proc Natl Acad Sci USA. 1999;96:12454–12458. doi: 10.1073/pnas.96.22.12454. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  17. Kodaira K, Takahashi R, Hirabayashi M, Suzuki T, Obinata M, Ueda M. Overexpression of c-myc induces apoptosis at the prophase of meiosis of rat primary spermatocytes. Mol Reprod Dev. 1996;45:403–410. doi: 10.1002/(SICI)1098-2795(199612)45:4<403::AID-MRD1>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar] · DOI
  18. Lansdorp PM, Verwoerd NP, van de Rijke FM, Dragowska V, Little MT, Dirks RW, Raap AK, Tanke HJ. Heterogeneity in telomere length of human chromosomes. Hum Mol Genet. 1996;5:685–691. doi: 10.1093/hmg/5.5.685. [DOI] [PubMed] [Google Scholar] · DOI
  19. Laroche T, Martin SG, Gotta M, Gorham HC, Pryde FE, Louis EJ, Gasser SM. Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres. Curr Biol. 1998;8:653–656. doi: 10.1016/s0960-9822(98)70252-0. [DOI] [PubMed] [Google Scholar] · DOI
  20. Lee SE, Moore JK, Holmes A, Umezu K, Kolodner RD, Haber JE. Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage. Cell. 1998b;94:399–409. doi: 10.1016/s0092-8674(00)81482-8. [DOI] [PubMed] [Google Scholar] · DOI
  21. Lundblad V, Szostak JW. A mutant with a defect in telomere elongation leads to senescence in yeast. Cell. 1989;57:633–643. doi: 10.1016/0092-8674(89)90132-3. [DOI] [PubMed] [Google Scholar] · DOI
  22. Naito T, Matsuura A, Ishikawa F. Circular chromosome formation in a fission yeast mutant defective in two ATM homologues. Nat Genet. 1998;20:203–206. doi: 10.1038/2517. [DOI] [PubMed] [Google Scholar] · DOI
  23. Nebel BR, Amarose AP, Hackett EM. Calendar of gametogenic development in the prepuberal male mouse. Science. 1961;134:832–833. doi: 10.1126/science.134.3482.832. [DOI] [PubMed] [Google Scholar] · DOI
  24. Nimmo ER, Pidoux AL, Perry PE, Allshire RC. Defective meiosis in telomere-silencing mutants of Schizosaccharomyces pombe. Nature. 1998;392:825–828. doi: 10.1038/33941. [DOI] [PubMed] [Google Scholar] · DOI
  25. Nugent CI, Bosco G, Ross LO, Evans SK, Salinger AP, Moore JK, Haber JE, Lundblad V. Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr Biol. 1998;8:657–660. doi: 10.1016/s0960-9822(98)70253-2. [DOI] [PubMed] [Google Scholar] · DOI
  26. Oakberg EF. Spermatogonial stem-cell renewal in the mouse. Anat Rec. 1971;169:515–531. doi: 10.1002/ar.1091690305. [DOI] [PubMed] [Google Scholar] · DOI
  27. Odorisio T, Rodriguez TA, Evans EP, Clarke AR, Burgoyne PS. The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53-independent apoptosis. Nat Genet. 1998;18:257–261. doi: 10.1038/ng0398-257. [DOI] [PubMed] [Google Scholar] · DOI
  28. Pittman DL, Cobb J, Schimenti KJ, Wilson LA, Cooper DM, Brignull E, Handel MA, Schimenti JC. Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog. Mol Cell. 1998;1:697–705. doi: 10.1016/s1097-2765(00)80069-6. [DOI] [PubMed] [Google Scholar] · DOI
  29. Prowse KR, Greider CW. Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci USA. 1995;92:4818–4822. doi: 10.1073/pnas.92.11.4818. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  30. Rockmill B, Roeder GS. Telomere-mediated chromosome pairing during meiosis in budding yeast. Genes Dev. 1998;12:2574–2586. doi: 10.1101/gad.12.16.2574. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  31. Scherthan H, Jerratsch M, Li B, Smith S, Hulten M, Lock T, de Lange T. Mammalian meiotic telomeres: protein composition and redistribution in relation to nuclear pores. Mol Biol Cell. 2000;11:4189–4203. doi: 10.1091/mbc.11.12.4189. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  32. Singer MS, Gottschling DE. TLC1: template RNA component of Saccharomyces cerevisiae telomerase. Science. 1994;266:404–409. doi: 10.1126/science.7545955. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  33. Welshons WJ, Gibson BH, Scandlyn BJ. Slide processing for the examination of male mammalian meiotic chromosomes. Stain Technol. 1962;37:1–5. doi: 10.3109/10520296209114560. [DOI] [PubMed] [Google Scholar] · DOI
  34. Wright WE, Piatyszek MA, Rainey WE, Byrd W, Shay JW. Telomerase activity in human germline and embryonic tissues and cells. Dev Genet. 1996;18:173–179. doi: 10.1002/(SICI)1520-6408(1996)18:2<173::AID-DVG10>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  35. Xu Y, Ashley T, Brainerd EE, Bronson RT, Meyn MS, Baltimore D. Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev. 1996;10:2411–2422. doi: 10.1101/gad.10.19.2411. [DOI] [PubMed] [Google Scholar] · DOI
  36. Yoshida K, Kondoh G, Matsuda Y, Habu T, Nishimune Y, Morita T. The mouse RecA-like gene Dmc1 is required for homologous chromosome synapsis during meiosis. Mol Cell. 1998;1:707–718. doi: 10.1016/s1097-2765(00)80070-2. [DOI] [PubMed] [Google Scholar] · DOI

Authors
Hemann, M. T., Rudolph, K. L., Strong, M. A., DePinho, R. A., Chin, L., & Greider, C. W.
Affiliations
  • Johns Hopkins University (US)
  • Harvard University (US)
ORCID
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2001-07
Volume
12
Issue
7
Pages
2023-2030
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
DOI
10.1091/mbc.12.7.2023
PMC
PMC55650
OpenAlex
W2171818443
Cited by
162
References
42
Citations by year
2026: 3 · 2023: 5 · 2022: 1 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 8 · 2014: 4 · 2013: 11 · 2012: 5
FWCI
8.37
Type
journal article
Language
en
Open access
Locations
  • Molecular Biology of the Cell (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • National Institutes of Health (5r01hd028317-05, 5r01hd034880-04, 5k08ar002104-04)
  • National Cancer Institute (CA-16519, P01CA016519)
  • National Institute of General Medical Sciences (T32GM007814, GM-07814)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08-AR02104)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 28317, HD-34880)
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
telomere dysfunction, germ cell apoptosis, meiotic progression, germ cell development, fertility defects, meiotic chromosome segregation, chromosomal abnormalities
MeSH terms
Animals, Male, Meiosis, Phenotype, Spermatozoa, Telomere, Apoptosis, 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