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Protoplasma

, Volume 255, Issue 5, pp 1477–1486 | Cite as

Replication timing of large Sorex granarius (Soricidae, Eulipotyphla) telomeres

  • Julia M. Minina
  • Tatjana V. Karamysheva
  • Nicolaj B. Rubtsov
  • Natalia S. Zhdanova
Original Article
  • 64 Downloads

Abstract

Previously, we described the unique feature of telomeric regions in Iberian shrew Sorex granarius: its telomeres have two ranges of size, very small (3.8 kb of telomeric repeats on average) and very large discontinuous telomeres (213 kb) interrupted with 18S rDNA. In this study, we have demonstrated extraordinary replication pattern of S. granarius large telomeres that have not been shown before in other studied mammal. Using the ReD-FISH procedure, we observed prolonged, through S period, large telomere replication. Furthermore, revealed ReD-FISH asymmetric signals were probably caused by partial replication of telomeres within an hour of 5-bromodeoxyuridine treatment due to the large size and special organization. We also found that in contrast to the telomeric halo from primary fibroblasts of bovine, mink, and common shrew, telomere halo of S. granarius consists of multiple loops bundled together, some of which contain rDNA. Here, we suggested several replicons firing possibly stochastic in each large telomere. Finally, we performed the TIF assay to reveal DNA damage responses at the telomeres, and along with TIF in nuclei, we found large bodies of telomeric DNA and ɤ-H2AX in the cytoplasm and on the surface of fibroblasts. We discuss the possibility of additional origin activation together with recombination-dependent replication pathways, mainly homologous recombination including BIR for replication fork stagnation overcoming and further S. granarius large telomere replication.

Keywords

Telomere replication ReD-FISH Halo Sorex granarius 

Abbreviations

FISH

Fluorescence in situ hybridization

ReD-FISH

Replication detargeting FISH

CO-FISH

Chromosome-oriented FISH

PNA probe

Peptide nucleic acid probe

FACS

Fluorescence-activated cell sorting

TIF

Telomere dysfunction-induced foci

HR

Homologous recombination

BIR

Break-induced replication

Notes

Acknowledgements

This work was supported by budget project no. 0324-2018-0019 of the Federal Research Center Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences.

The experiments comply with the current laws of Russian Federation country in which they were performed.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Studies with human or animal

All animal studies were undertaken with prior approval from Interinstitutional Bioethical Committee of ICG SB RAS.

This article does not contain any studies with human or animal subjects performed by the any of the authors.

References

  1. Anachkova B, Djeliova V, Russev G (2005) Nuclear matrix support of DNA replication. J Cell Biochem 96(5):951–961.  https://doi.org/10.1002/jcb.20610 CrossRefPubMedGoogle Scholar
  2. Arnoult N, Schluth-Bolard C, Letessier A, Drascovic I, Bouarich-Bourimi R, Campisi J, Kim SH, Boussouar A, Ottaviani A, Magdinier F, Gilson E, Londoño-Vallejo A (2010) Replication timing of human telomeres is chromosome arm-specific, influenced by subtelomeric structures and connected to nuclear localization. PLoS Genet 6(4):e1000920.  https://doi.org/10.1371/journal.pgen.1000920 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Biltueva L, Vorobieva N, Perelman P, Trifonov V, Volobouev V, Panov V, Ilyashenko V, Onischenko S, O’Brien P, Yang F, Ferguson-Smith M, Graphodatsky A (2011) Karyotype evolution of Eulipotyphla (Insectivora): the genome homology of seven Sorex species revealed by comparative chromosome painting and banding data. Cytogenet Genome Res 135(1):51–64.  https://doi.org/10.1159/000330577 CrossRefPubMedGoogle Scholar
  4. Blow JJ, Ge XQ (2008) Replication forks, chromatin loops and dormant replication origins. Genome Biol 9(12):244.  https://doi.org/10.1186/gb-2008-9-12-244 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bosco G, Haber JE (1998) Chromosome break-induced DNA replication leads to nonreciprocal translocations and telomere capture. Genetics 150(3):1037–1047PubMedPubMedCentralGoogle Scholar
  6. Buongiorno-Nardelli M, Micheli G, Carri MT, Marilley M (1982) A relationship between replicon size and supercoiled loop domains in the eukaryotic genome. Nature 298(5869):100–102CrossRefPubMedGoogle Scholar
  7. Conomos D, Stutz MD, Hills M, Neumann AA, Bryan TM, Reddel RR, Pickett HA (2012) Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells. J Cell Biol 199(6):893–906.  https://doi.org/10.1083/jcb.201207189 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Courbet S, Gay S, Arnoult N, Wronka G, Anglana M, Brison O, Debatisse M (2008) Replication fork movement sets chromatin loop size and origin choice in mammalian cells. Nature 455(7212):557–560.  https://doi.org/10.1038/nature07233 CrossRefPubMedGoogle Scholar
  9. Darzynkiewicz Z, Halicka HD, Zhao H, Podhorecka M (2011) Cell synchronization by inhibitors of DNA replication induces replication stress and DNA damage response: analysis by flow cytometry. Methods Mol Biol 761:85–96.  https://doi.org/10.1007/978-1-61779-182-6_6 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Drosopoulos WC, Kosiyatrakul ST, Yan Z, Calderano SG, Schildkraut CL (2012) Human telomeres replicate using chromosomes specific, rather than universal, replication programs. J Cell Biol 197(2):253–266.  https://doi.org/10.1083/jcb.201112083 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Drosopoulos WC, Kosiyatrakul ST, Schildkraut CL (2015) BLM helicase facilitates telomere replication during leading strand synthesis of telomeres. J Cell Biol 210(2):191–208.  https://doi.org/10.1083/jcb.201410061 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Elcock LS, Bridger JM (2010) Fluorescence in situ hybridization on DNA halo preparations and extended chromatin fibres. Methods Mol Biol 659:21–31.  https://doi.org/10.1007/978-1-60761-789-1_2 CrossRefPubMedGoogle Scholar
  13. Gerdes MG, Carter KC, Moen PT Jr, Lawrence JB (1994) Dynamic changes in the higher-level chromatin organization of specific sequences revealed by in situ hybridization to nuclear halos. J Cell Biol 126(2):289–304CrossRefPubMedGoogle Scholar
  14. Gilson E, Geli V (2007) How telomeres are replicated. Nat Rev Mol Cell Biol 8:825–838.  https://doi.org/10.1038/nrm2259 CrossRefPubMedGoogle Scholar
  15. Halicka D, Zhao H, Li J et al (2017) DNA damage response resulting from replication stress induced by synchronization of cells by inhibitors of DNA replication: analysis by flow cytometry. Cell Cycle Synchronization: Methods Protoc 1524:107–119.  https://doi.org/10.1007/978-1-4939-6603-5_7 CrossRefGoogle Scholar
  16. Kim JC, Harris ST, Dinter T, Shah KA, Mirkin SM (2017) The role of break-induced replication in large-scale expansions of (CAG)n/(CTG)n repeats. Nat Struct Mol Biol 24:55–60.  https://doi.org/10.1038/nsmb.3334 CrossRefPubMedGoogle Scholar
  17. Kipling D, Cooke HJ (1990) Hypervariable ultra-long telomeres in mice. Nature 347(6291):400–402.  https://doi.org/10.1038/347400a0 CrossRefPubMedGoogle Scholar
  18. Llorente B, Smith CE, Symington LS (2008) Break-induced replication: what is it and what is it for? Cell Cycle 7:859–864.  https://doi.org/10.4161/cc.7.7.5613 CrossRefPubMedGoogle Scholar
  19. Londono-Vallejo JA, Der-Sarkissian H, Cazes L et al (2004) Alternative lengthening of telomeres is characterized by high rates of telomeric exchange. Cancer Res 64(7):2324–2327.  https://doi.org/10.1158/0008-5472 CrossRefPubMedGoogle Scholar
  20. Lydeard JR, Lipkin-Moore Z, Sheu YJ, Stillman B, Burgers PM, Haber JE (2010) Break-induced replication requires all essential DNA replication factors except those specific for pre-RC assembly. Genes Dev 24(11):1133–1144.  https://doi.org/10.1101/gad.1922610 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Malygin AA, Graĭfer DM, Zenkova MA et al (1992) Affinity modification of 80S ribosomes from human placenta by derivatives of tri- and hexauridylates as mRNA analogs. Mol Biol (Mosk) 26(2):369–377Google Scholar
  22. Martin M, Terradas M, Hernandez L, Genesca A (2014) ɤH2AX foci on apparently intact mitotic chromosomes: not signatures of misrejoining events but signals of unresolved DNA damage. Cell Cycle 13(19):3026–3036.  https://doi.org/10.4161/15384101.2014.947786 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Matsui A, Ihara T, Suda H, Mikami H, Semba K (2013) Gene amplification: mechanisms and involvement in cancer. BioMol Concepts 4(6):567–582.  https://doi.org/10.1515/bmc-2013-0026 CrossRefPubMedGoogle Scholar
  24. Nakamura H, Morita T, Sato C (1986) Structural organizations of replicon domains during DNA synthetic phase in the mammalian nucleus. Exp Cell Res 165(2):291–297CrossRefPubMedGoogle Scholar
  25. Olovnikov AM (1973) A theory of marginotomy: the incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 41(1):181–190CrossRefPubMedGoogle Scholar
  26. Raghuraman MK, Winzeler EA, Collingwood D, Hunt S, Wodicka L, Conway A, Lockhart DJ, Davis RW, Brewer BJ, Fangman WL (2001) Replication dynamics of the yeast genome. Science 294(5540):115–121.  https://doi.org/10.1126/science.294.5540.115 CrossRefPubMedGoogle Scholar
  27. Razin SV (2001) The nuclear matrix and chromosomal DNA loops: is there correlation between partitioning of the genome into loops and functional domains? Cell Mol Biol Lett 6(1):59–69PubMedGoogle Scholar
  28. Rhind N (2006) DNA replication timing: random thoughts about origin firing. Nat Cell Biol 8(12):1313–1316.  https://doi.org/10.1038/ncb1206-1313 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Rivera-Mulia JC, Hernandez-Muñoz R, Martinez F, Aranda-Anzaldo A (2011) DNA moves sequentially towards the nuclear matrix during DNA replication in vivo. BMC Cell Biol 12(3):3.  https://doi.org/10.1186/1471-2121-12-3 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998) DNA double stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273(10):5858–5868CrossRefPubMedGoogle Scholar
  31. Rosner M, Schupany K, Hengstschlager M (2013) Merging high-quality biochemical fractionation with a refined flow cytometry approach to monitor nucleocytoplasmic protein expression throughout the unperturbed mammalian cell cycle. Nat Protoc 8:602–626.  https://doi.org/10.1038/nprot.2013.011 CrossRefPubMedGoogle Scholar
  32. Roumelioti FM, Sotiriou SK, Katsini V, Chiourea M, Halazonetis TD, Gagos S (2016) Alternative lengthening of human telomeres is a conservative DNA replication process with features of break-induced replication. EMBO Rep 17(12):1731–1737.  https://doi.org/10.15252/embr.201643169 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Rubtsov NB, Zhdanova NS (2017) The replicative detargeting FISH (ReD-FISH) technique in studies of telomere replication. In: Liehr T (ed) Fluorescence in situ hybridization (FISH): Application guide. Springer, pp 159–168.  https://doi.org/10.1007/978-3-662-52959-1_16
  34. Sakofsky CJ, Malkova A (2017) Break induced replication in eukaryotes: mechanisms, functions, and consequences. Crit Rev Biochem Mol Biol 52(4):395–413.  https://doi.org/10.1080/10409238.2017.1314444 CrossRefPubMedGoogle Scholar
  35. Samassekou O, Gadji M, Drouin R, Yan J (2010) Sizing the ends: normal length of human telomeres. Ann Anat 192(5):284–291.  https://doi.org/10.1016/j.aanat.2010.07.005 CrossRefPubMedGoogle Scholar
  36. Sobinoff AP, Pickett HA (2017) Alternative lengthening of telomeres: DNA repair pathways converge. Trends Genet 33(12):921–932.  https://doi.org/10.1016/j.tig.2017.09.003 CrossRefPubMedGoogle Scholar
  37. Tacconi EM, Tarsounas M (2015) How homologous recombination maintains telomere integrity. Chromosoma 124(2):119–130.  https://doi.org/10.1007/s00412-014-0497-2 CrossRefPubMedGoogle Scholar
  38. Vaughn JP, Dijkwel PA, Mullenders LH, Hamlin JL (1990) Replication forks are associated with the nuclear matrix. Nucleic Acids Res 18(8):1965–1969CrossRefPubMedPubMedCentralGoogle Scholar
  39. Wiegant J, Kalle W, Mullenders L, Brookes S, Hoovers JMN, Dauwerse JG, van Ommen GJB, Raap AK (1992) High-resolution in situ hybridization using DNA halo preparations. Hum Mol Genet 1(8):587–591CrossRefPubMedGoogle Scholar
  40. Zhdanova NS, Karamisheva TV, Minina J, Astakhova NM, Lansdorp P, Kammori M, Rubtsov NB, Searle JB (2005) Unusual distribution pattern of telomeric repeats in the shrews Sorex araneus and Sorex granarius. Chromosom Res 13(6):617–625.  https://doi.org/10.1007/s10577-005-0988-3 CrossRefGoogle Scholar
  41. Zhdanova NS, Minina JM, Karamisheva TV, Draskovic I, Rubtsov NB, Londoño-Vallejo JA (2007) The very long telomeres in Sorex granarius (Soricidae, Eulipothyphla) contain ribosomal DNA. Chromosom Res 15(7):881–890.  https://doi.org/10.1007/s10577-007-1170-x CrossRefGoogle Scholar
  42. Zhdanova NS, Minina JM, Rubtsov NB (2012) Mammalian telomere biology. Mol Biol (Mosk) 46(4):539–555CrossRefGoogle Scholar
  43. Zhdanova NS, Draskovic I, Minina JM, Karamysheva TV, Novo CL, Liu WY, Porreca RM, Gibaud A, Zvereva ME, Skvortsov DA, Rubtsov NB, Londono-Vallejo A (2014) Recombinogenic telomeres in diploid fibroblast cells Sorex granarius (Soricidae, Eulipotyphla). Mol Cell Biol 34(15):2786–2799.  https://doi.org/10.1128/MCB.01697-13 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Zou Y, Gryaznov SM, Shay JW, Wright WE, Cornforth MN (2004) Asynchronous replication timing of telomeres at opposite arms of mammalian chromosomes. Proc Natl Acad Sci U S A 101(35):12928–12933.  https://doi.org/10.1073/pnas.0404106101 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.The Federal Research Center Institute of Cytology and Genetics of SB RASNovosibirskRussia

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