A balance between elongation and trimming regulates telomere stability in stem cells

Nature Structural and Molecular Biology

Volumn 24, Issue 1, 2017, Pages 30-39

  Rivera, Teresa ^a   Haggblom, Candy ^a   Cosconati, Sandro ^b   Karlseder, Jan ^a  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^b SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CIRCULAR DNA; DOUBLE STRANDED DNA; NIBRIN; SINGLE STRANDED DNA; TELOMERASE; XRCC3 PROTEIN; CELL CYCLE PROTEIN; DNA BINDING PROTEIN; NBN PROTEIN, HUMAN; NUCLEAR PROTEIN; X-RAY REPAIR CROSS COMPLEMENTING PROTEIN 3;

5' UNTRANSLATED REGION; ARTICLE; CELL DIFFERENTIATION; CELL DIVISION; CELL STRESS; CONTROLLED STUDY; DNA REPLICATION; HOMOLOGOUS RECOMBINATION; HUMAN; HUMAN CELL; HUMAN EMBRYONIC STEM CELL; INDUCED PLURIPOTENT STEM CELL; INTRACELLULAR SIGNALING; PRIORITY JOURNAL; REGULATORY MECHANISM; TELOMERE ELONGATION; TELOMERE HOMEOSTASIS; TELOMERE LENGTH; TELOMERE SHORTENING; TELOMERE TRIMMING; CELL CULTURE; GENETICS; METABOLISM; NUCLEAR REPROGRAMMING; NUCLEOTIDE REPEAT; TELOMERE;

CELL CYCLE PROTEINS; CELLS, CULTURED; CELLULAR REPROGRAMMING; DNA REPLICATION; DNA-BINDING PROTEINS; HUMAN EMBRYONIC STEM CELLS; HUMANS; INDUCED PLURIPOTENT STEM CELLS; NUCLEAR PROTEINS; REPETITIVE SEQUENCES, NUCLEIC ACID; TELOMERE; TELOMERE HOMEOSTASIS;

EID: 85002271156     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.3335     Document Type: Article

References (58)

1. de Lange, T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 19, 2100-2110 (2005).
2. Makarov, V.L., Hirose, Y. & Langmore, J.P. Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 88, 657-666 (1997).
3. Griffith, J.D. et al. Mammalian telomeres end in a large duplex loop. Cell 97, 503-514 (1999).
4. de Lange, T. T-loops and the origin of telomeres. Nat. Rev. Mol. Cell Biol. 5, 323-329 (2004).
5. Doksani, Y., Wu, J.Y., de Lange, T. & Zhuang, X. Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell 155, 345-356 (2013).
6. Olovnikov, A.M. 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, 181-190 (1973).
7. Watson, J.D. Origin of concatemeric T7 DNA. Nat. New Biol. 239, 197-201 (1972).
8. Wu, P., Takai, H. & de Lange, T. Telomeric 3' overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST. Cell 150, 39-52 (2012).
9. Kim, N.W. et al. Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011-2015 (1994).
10. Wright, W.E., Piatyszek, M.A., Rainey, W.E., Byrd, W. & Shay, J.W. Telomerase activity in human germline and embryonic tissues and cells. Dev. Genet. 18, 173-179 (1996).
11. Cohen, S.B. et al. Protein composition of catalytically active human telomerase from immortal cells. Science 315, 1850-1853 (2007).
12. Bryan, T.M., Englezou, A., Dalla-Pozza, L., Dunham, M.A. & Reddel, R.R. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat. Med. 3, 1271-1274 (1997).
13. Londoño-Vallejo, J.A., Der-Sarkissian, H., Cazes, L., Bacchetti, S. & Reddel, R.R. Alternative lengthening of telomeres is characterized by high rates of telomeric exchange. Cancer Res. 64, 2324-2327 (2004).
14. Yeager, T.R. et al. Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer Res. 59, 4175-4179 (1999).
15. Bryan, T.M., Englezou, A., Gupta, J., Bacchetti, S. & Reddel, R.R. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J. 14, 4240-4248 (1995).
16. Oganesian, L. & Karlseder, J. Mammalian 5' C-rich telomeric overhangs are a mark of recombination-dependent telomere maintenance. Mol. Cell 42, 224-236 (2011).
17. Tokutake, Y. et al. Extra-chromosomal telomere repeat DNA in telomerase-negative immortalized cell lines. Biochem. Biophys. Res. Commun. 247, 765-772 (1998).
18. Cesare, A.J. & Griffith, J.D. Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous T-loops. Mol. Cell. Biol. 24, 9948-9957 (2004).
19. Henson, J.D. et al. DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity. Nat. Biotechnol. 27, 1181-1185 (2009).
20. Sharpless, N.E. & DePinho, R.A. How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol. 8, 703-713 (2007).
21. Aubert, G. Telomere dynamics and aging. Prog. Mol. Biol. Transl. Sci. 125, 89-111 (2014).
22. Zeng, S. et al. Telomerase-mediated telomere elongation from human blastocysts to embryonic stem cells. J. Cell Sci. 127, 752-762 (2014).
23. Batista, L.F. et al. Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature 474, 399-402 (2011).
24. Raices, M. et al. C. elegans telomeres contain G-strand and C-strand overhangs that are bound by distinct proteins. Cell 132, 745-757 (2008).
25. Pickett, H.A., Cesare, A.J., Johnston, R.L., Neumann, A.A. & Reddel, R.R. Control of telomere length by a trimming mechanism that involves generation of t-circles. EMBO J. 28, 799-809 (2009).
26. Pickett, H.A., Henson, J.D., Au, A.Y., Neumann, A.A. & Reddel, R.R. Normal mammalian cells negatively regulate telomere length by telomere trimming. Hum. Mol. Genet. 20, 4684-4692 (2011).
27. Nabetani, A. & Ishikawa, F. Unusual telomeric DNAs in human telomerase-negative immortalized cells. Mol. Cell. Biol. 29, 703-713 (2009).
28. Wang, R.C., Smogorzewska, A. & de Lange, T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119, 355-368 (2004).
29. O'Sullivan, R.J. et al. Rapid induction of alternative lengthening of telomeres by depletion of the histone chaperone ASF1. Nat. Struct. Mol. Biol. 21, 167-174 (2014).
30. Marion, R.M. et al. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell 4, 141-154 (2009).
31. Agarwal, S. et al. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464, 292-296 (2010).
32. Wang, F. et al. Molecular insights into the heterogeneity of telomere reprogramming in induced pluripotent stem cells. Cell Res. 22, 757-768 (2012).
33. Panopoulos, A.D. et al. Rapid and highly efficient generation of induced pluripotent stem cells from human umbilical vein endothelial cells. PLoS One 6, e19743 (2011).
34. Panopoulos, A.D. et al. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 22, 168-177 (2012).
35. Poole, L.A. et al. SMARCAL1 maintains telomere integrity during DNA replication. Proc. Natl. Acad. Sci. USA 112, 14864-14869 (2015).
36. Rizzo, A. et al. Stabilization of quadruplex DNA perturbs telomere replication leading to the activation of an ATR-dependent ATM signaling pathway. Nucleic Acids Res. 37, 5353-5364 (2009).
37. Lin, W. et al. Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity. EMBO J. 32, 1425-1439 (2013).
38. Thangavel, S. et al. DNA2 drives processing and restart of reversed replication forks in human cells. J. Cell Biol. 208, 545-562 (2015).
39. Sfeir, A. et al. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138, 90-103 (2009).
40. Oganesian, L. & Karlseder, J. 5' C-rich telomeric overhangs are an outcome of rapid telomere truncation events. DNA Repair (Amst.) 12, 238-245 (2013).
41. Compton, S.A., Choi, J.H., Cesare, A.J., Ozgür, S. & Griffith, J.D. Xrcc3 and Nbs1 are required for the production of extrachromosomal telomeric circles in human alternative lengthening of telomere cells. Cancer Res. 67, 1513-1519 (2007).
42. Cesare, A.J. & Reddel, R.R. Alternative lengthening of telomeres: models, mechanisms and implications. Nat. Rev. Genet. 11, 319-330 (2010).
43. Niida, H. et al. Telomere maintenance in telomerase-deficient mouse embryonic stem cells: characterization of an amplified telomeric DNA. Mol. Cell. Biol. 20, 4115-4127 (2000).
44. Wang, Y. et al. An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres. Proc. Natl. Acad. Sci. USA 102, 10256-10260 (2005).
45. Zalzman, M. et al. Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature 464, 858-863 (2010).
46. Sexton, A.N. et al. Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation. Genes Dev. 28, 1885-1899 (2014).
47. Winkler, T. et al. Defective telomere elongation and hematopoiesis from telomerase-mutant aplastic anemia iPSCs. J. Clin. Invest. 123, 1952-1963 (2013).
48. Moon, D.H. et al. Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component. Nat. Genet. 47, 1482-1488 (2015).
49. Gu, B.W. et al. Impaired telomere maintenance and decreased canonical WNT signaling but normal ribosome biogenesis in induced pluripotent stem cells from X-linked dyskeratosis congenita patients. PLoS One 10, e0127414 (2015).
50. Verdun, R.E. & Karlseder, J. The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127, 709-720 (2006).
51. Zhong, Z.H. et al. Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. J. Biol. Chem. 282, 29314-29322 (2007).
52. Takata, M. et al. Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs. Mol. Cell. Biol. 21, 2858-2866 (2001).
53. Dumon-Jones, V. et al. Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Cancer Res. 63, 7263-7269 (2003).
54. Gilson, E. & Géli, V. How telomeres are replicated. Nat. Rev. Mol. Cell Biol. 8, 825-838 (2007).
55. Martínez, P. et al. Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice. Genes Dev. 23, 2060-2075 (2009).
56. Bétous, R. et al. SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication. Genes Dev. 26, 151-162 (2012).
57. Ahuja, A.K. et al. A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. Nat. Commun. 7, 10660 (2016).
58. Göhring, J., Fulcher, N., Jacak, J. & Riha, K. TeloTool: a new tool for telomere length measurement from terminal restriction fragment analysis with improved probe intensity correction. Nucleic Acids Res. 42, e21 (2014).