Chromosome ends as adaptive beginnings: the potential role of dysfunctional telomeres in subtelomeric evolvability

Review

Abstract

Telomeres serve as protective caps that help the cell differentiate between the naturally occurring ends of chromosomes and double-stranded breaks. When telomere capping function becomes compromised, chromosome ends are subjected to elevated rates of chromosome alterations. These effects can be particularly dramatic in the telomere-adjacent subtelomeric region. While the catastrophic impact of severe telomere dysfunction on genome stability has been well documented, the adaptive telomere failure hypothesis considers an alternative role telomere dysfunction may play in adaptive evolution. This hypothesis suggests that low levels of telomere failure, induced by certain environmental stresses, can lead to elevated subtelomeric recombination. Mutational loss, duplication, or modification of subtelomeric contingency genes could ultimately facilitate adaptation by generating novel mutants better able to survive environmental stress. In this perspective, we discuss recent work that examined mild telomere dysfunction and its role in altering the adaptive potential of subtelomeric genes.

Keywords

Break-induced replication Mild telomere dysfunction Subtelomere Yeast β-Galactosidase 

References

  1. Anand RP, Lovett ST, Haber JE (2013) Break-induced DNA replication. Cold Spring Harb Perspect Biol 5(12):a010397CrossRefPubMedPubMedCentralGoogle Scholar
  2. Barry JD, Ginger ML, Burton P, McCulloch R (2003) Why are parasite contingency genes often associated with telomeres. Int J Parasitol 33:29–45CrossRefPubMedGoogle Scholar
  3. Bechard LH, Jamieson N, McEachern MJ (2011) Recombination can cause telomere elongations as well as truncations deep within telomeres in wild-type Kluyveromyces lactis cells. Eukaryot cell 10(2):226–236CrossRefPubMedPubMedCentralGoogle Scholar
  4. Booth C, Griffith E, Brady G, Lydall D (2001) Quantitative amplification of single-stranded DNA (QAOS) demonstrates that cdc13-1 mutants generate ssDNA in a telomere to centromere direction. Nucleic Acids Res 29:4414–4422CrossRefPubMedPubMedCentralGoogle Scholar
  5. Brown CA, Murray AW, Verstrepen KJ (2010) Rapid expansion and functional divergence of subtelomeric gene families in yeasts. Curr Biol 20:895–903CrossRefPubMedPubMedCentralGoogle Scholar
  6. Cheung I, Schertzer M, Rose A, Lansdorp PM (2006) High incidence of rapid telomere loss in telomerase-deficient Caenorhabditis elegans. Nucleic Acids Res 34:96–103CrossRefPubMedPubMedCentralGoogle Scholar
  7. Craven RJ, Petes TD (1999) Dependence of the regulation of telomere length on the type of subtelomeric repeat in the yeast Saccharomyces cerevisiae. Genetics 152:1531–1541PubMedPubMedCentralGoogle Scholar
  8. Deem A, Keszthelyi A, Blackgrove T, Vayl A, Coffey B, Mathur R, Chabes A, Malkova A (2011) Break-induced replication is highly inaccurate. PLoS Biol 9(2):e10000594CrossRefGoogle Scholar
  9. Dilley RL, Verma P, Cho NW, Winters HD, Anne R, Greenberg RA (2017) Break-induced telomere synthesis underlies alternative telomere maintenance. Nature 539:54–58CrossRefGoogle Scholar
  10. Durdíková K, Chovanec M (2017) Regulation of non-homologous end joining via post-translational modifications of components of the ligation step. Curr Genet 63(4):591–605CrossRefPubMedGoogle Scholar
  11. Gadaleta MC, González-Medina A, Noguchi E (2016) Timeless protection of telomeres. Curr Genet 62:725–730CrossRefPubMedPubMedCentralGoogle Scholar
  12. Garvik B, Carson M, Hartwell L (1995) Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol Cell Biol 15:6128–6138CrossRefPubMedPubMedCentralGoogle Scholar
  13. Gottschling DE, Aparicio OM, Billington BL, Zakian VA (1990) Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell 63:751–762CrossRefPubMedGoogle Scholar
  14. Hackett JA, Greider CW (2003) End resection initiates genomic instability in the absence of telomerase. Mol Cell Biol 23:8450–8461CrossRefPubMedPubMedCentralGoogle Scholar
  15. Hackett JA, Feldser DM, Greider CW (2001) Telomere dysfunction increases mutation rate and genomic instability. Cell 106:275–286CrossRefPubMedGoogle Scholar
  16. Kaul Z, Cesare AJ, Huschtscha LI, Neumann AA, Reddel RR (2012) Five dysfunctional telomeres predict onset of senescence in human cells. EMBO Rep 13:52–59CrossRefGoogle Scholar
  17. Larson DD, Spangler EA, Blackburn EH (1987) Dynamics of telomere length variation in Tetrahymena thermophila. Cell 50:477–483CrossRefPubMedGoogle Scholar
  18. Li B (2015) DNA double-strand breaks and telomeres play important roles in Trypanosoma brucei antigenic variation. Eukaryot Cell 14:196–205CrossRefPubMedPubMedCentralGoogle Scholar
  19. Li B, Lustig AJ (1996) A novel mechanism for telomere size control in Saccharomyces cerevisiae. Genes Dev 10:1310–1326CrossRefPubMedGoogle Scholar
  20. Linardopoulou EV, Williams EM, Fan Y, Friedman C, Young JM, Trask BJ (2005) Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication. Nature 437:94–100CrossRefPubMedPubMedCentralGoogle Scholar
  21. Lue NF, Yu EY (2017) Telomere recombination pathways: tales of several unhappy marriages. Curr Genet 63.3:401–409CrossRefGoogle Scholar
  22. Maciejowski J, Li Y, Bosco N, Campbell PJ, Lange T, De (2015) Chromothripsis and kataegis induced by telomere crisis. Cell 163:1641–1654CrossRefPubMedPubMedCentralGoogle Scholar
  23. Maciejowski J, Lange T de (2017) Telomeres in cancer: tumor suppression and genome instability. Nat Rev Mol Cell Biol 18:175–186CrossRefPubMedPubMedCentralGoogle Scholar
  24. Mason JMO, McEachern MJ (2017) Mild telomere dysfunction as a force for altering the adaptive potential of subtelomeric genes. Genetics.  https://doi.org/10.1534/genetics.117.300607 Google Scholar
  25. McEachern MJ (2008) Telomeres: guardians of genomic integrity or double agents of evolution. In: Nosek J, Tomáška L, (eds) Origin and evolution of telomeres. Landes Bioscience, Austin, pp 100–113Google Scholar
  26. McEachern MJ, Iyer S (2001) Short telomeres in yeast are highly recombinogenic. Mol Cell 7:695–704CrossRefPubMedGoogle Scholar
  27. Mefford HC, Trask BJ (2002) The complex structure and dynamic evolution of human subtelomeres. Nat Rev Genet 3:91–102CrossRefPubMedGoogle Scholar
  28. Mieczkowski PA, Mieczkowska JO, Dominska M, Petes TD (2003) Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci USA 100:10854–10859CrossRefPubMedPubMedCentralGoogle Scholar
  29. Millet C, Makovets S (2016) Aneuploidy as a mechanism of adaptation to telomerase insufficiency. Curr Genet 62(3):557–564CrossRefPubMedPubMedCentralGoogle Scholar
  30. Myler PJ, Aline RF, Scholler JK, Stuart KD (1988) Changes in telomere length associated with antigenic variation in Trypanosoma brucei. Mol Biochem Parasitol 29:243–250CrossRefPubMedGoogle Scholar
  31. O’Sullivan RJ, Karlseder J (2010) Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol 11:171–181CrossRefPubMedPubMedCentralGoogle Scholar
  32. Ottaviani A, Gilson E, Magdinier F (2008) Telomeric position effect: from the yeast paradigm to human pathologies. Biochimie 90:93–107CrossRefPubMedGoogle Scholar
  33. Podlevsky JD, Chen JJL (2012) It all comes together at the ends: telomerase structure, function, and biogenesis. Mutat Res Fundam Mol Mech Mutagen 730:3–11CrossRefGoogle Scholar
  34. Pryde FE, Gorham HZ, Louise EJ (1997) Chromosome ends: all the same under their caps. Curr Opin Genet Dev 7:822–828CrossRefPubMedGoogle Scholar
  35. Rudd MK, Friedman C, Parghi SS, Linardopoulou EV, Hsu L, Trask BJ (2007) Elevated rates of sister chromatid exchange at chromosome ends. PLoS Genet 3:0319–0323CrossRefGoogle Scholar
  36. Sakofsky CJ, Ayyar S, Deem AK, Chung WH, Ira G, Malkova A (2015) Translesion polymerases drive microhomology-mediated break-induced replication leading to complex chromosomal rearrangements. Mol Cell 60:860–872CrossRefPubMedPubMedCentralGoogle Scholar
  37. Shay JW (2016) Role of telomeres and telomerase in aging and cancer. Cancer Discov 6:584–593CrossRefPubMedPubMedCentralGoogle Scholar
  38. Vermeesch JR, Williams D, Price CM (1993) Telomere processing in Euplotes. Nucleic Acids Res 21:5366–5371CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of GeneticsUniversity of GeorgiaAthensUSA
  2. 2.Q2 SolutionsMorrisvilleUSA

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