Modification of Subtelomeric DNA

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2004 May 4

PMID 15121873

Citations 20

Authors

Susanne Steinert

Jerry W Shay

Woodring E Wright

Affiliations

Soon will be listed here.

Abstract

There is a discrepancy in telomere length as measured by signal intensity of telomere restriction fragments on gels and fluorescence in situ hybridization analysis. This difference has been ascribed to the X-region, a segment of subtelomeric DNA that is resistant to being cut by restriction enzymes. To explore the nature of this region, we analyzed the digestibility of an artificial seeded telomere in HeLa cells as well as the Xp/Yp autosomal telomere in human BJ fibroblasts. We found that there is a substantial fraction of subtelomeric DNA containing restriction sites that is not digested with enzymes such as EcoRI, NlaIII, and SphI. Comparison of methylation-sensitive and -resistant enzymes excluded the possibility of the X-region being maintained by DNA methylation. We show that the X-region represents a variable domain whose size changes with telomere length, and neither non-TTAGGG sequences nor cytidine methylation can adequately explain the size of the X-region.

Citing Articles

Relationship between aging and control of metabolic syndrome with telomere shortening: a cross-sectional study.

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Buildup from birth onward of short telomeres in human hematopoietic cells.

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The Alteration of Subtelomeric DNA Methylation in Aging-Related Diseases.

Hu H, Li B, Duan S Front Genet. 2019; 9:697.

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Targeting Telomerase and ATRX/DAXX Inducing Tumor Senescence and Apoptosis in the Malignant Glioma.

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References

Yoder J, Walsh C, Bestor T . Cytosine methylation and the ecology of intragenomic parasites. Trends Genet. 1997; 13(8):335-40. DOI: 10.1016/s0168-9525(97)01181-5. View

Bryan T, Marusic L, Bacchetti S, Namba M, Reddel R . The telomere lengthening mechanism in telomerase-negative immortal human cells does not involve the telomerase RNA subunit. Hum Mol Genet. 1997; 6(6):921-6. DOI: 10.1093/hmg/6.6.921. View

Wright W, Tesmer V, Huffman K, Levene S, Shay J . Normal human chromosomes have long G-rich telomeric overhangs at one end. Genes Dev. 1997; 11(21):2801-9. PMC: 316649. DOI: 10.1101/gad.11.21.2801. View

Van Leeuwen F, Taylor M, Mondragon A, Moreau H, Gibson W, Kieft R . beta-D-glucosyl-hydroxymethyluracil is a conserved DNA modification in kinetoplastid protozoans and is abundant in their telomeres. Proc Natl Acad Sci U S A. 1998; 95(5):2366-71. PMC: 19348. DOI: 10.1073/pnas.95.5.2366. View

Hultdin M, Gronlund E, Norrback K, Just T, Roos G . Telomere analysis by fluorescence in situ hybridization and flow cytometry. Nucleic Acids Res. 1998; 26(16):3651-6. PMC: 147775. DOI: 10.1093/nar/26.16.3651. View

Griffith J, Comeau L, Rosenfield S, Stansel R, Bianchi A, Moss H . Mammalian telomeres end in a large duplex loop. Cell. 1999; 97(4):503-14. DOI: 10.1016/s0092-8674(00)80760-6. View

Coleman J, Baird D, Royle N . The plasticity of human telomeres demonstrated by a hypervariable telomere repeat array that is located on some copies of 16p and 16q. Hum Mol Genet. 1999; 8(9):1637-46. DOI: 10.1093/hmg/8.9.1637. View

Smilenov L, Dhar S, Pandita T . Altered telomere nuclear matrix interactions and nucleosomal periodicity in ataxia telangiectasia cells before and after ionizing radiation treatment. Mol Cell Biol. 1999; 19(10):6963-71. PMC: 84691. DOI: 10.1128/MCB.19.10.6963. View

Baird D, Coleman J, Rosser Z, Royle N . High levels of sequence polymorphism and linkage disequilibrium at the telomere of 12q: implications for telomere biology and human evolution. Am J Hum Genet. 2000; 66(1):235-50. PMC: 1288329. DOI: 10.1086/302721. View

10.

Ouellette M, Liao M, Herbert B, Johnson M, Holt S, Liss H . Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase. J Biol Chem. 2000; 275(14):10072-6. DOI: 10.1074/jbc.275.14.10072. View

11.

Ramsahoye B, Biniszkiewicz D, Lyko F, Clark V, Bird A, Jaenisch R . Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci U S A. 2000; 97(10):5237-42. PMC: 25812. DOI: 10.1073/pnas.97.10.5237. View

12.

Baur J, Zou Y, Shay J, Wright W . Telomere position effect in human cells. Science. 2001; 292(5524):2075-7. DOI: 10.1126/science.1062329. View

13.

Mefford H, Trask B . The complex structure and dynamic evolution of human subtelomeres. Nat Rev Genet. 2002; 3(2):91-102. DOI: 10.1038/nrg727. View

14.

Wright W, Shay J . Historical claims and current interpretations of replicative aging. Nat Biotechnol. 2002; 20(7):682-8. DOI: 10.1038/nbt0702-682. View

15.

Koering C, Pollice A, Zibella M, Bauwens S, Puisieux A, Brunori M . Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity. EMBO Rep. 2002; 3(11):1055-61. PMC: 1307600. DOI: 10.1093/embo-reports/kvf215. View

16.

Gruenbaum Y, Stein R, Cedar H, Razin A . Methylation of CpG sequences in eukaryotic DNA. FEBS Lett. 1981; 124(1):67-71. DOI: 10.1016/0014-5793(81)80055-5. View

17.

Moyzis R, Buckingham J, Cram L, Dani M, Deaven L, Jones M . A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci U S A. 1988; 85(18):6622-6. PMC: 282029. DOI: 10.1073/pnas.85.18.6622. View

18.

Allshire R, Dempster M, Hastie N . Human telomeres contain at least three types of G-rich repeat distributed non-randomly. Nucleic Acids Res. 1989; 17(12):4611-27. PMC: 318019. DOI: 10.1093/nar/17.12.4611. View

19.

de Lange T, Shiue L, Myers R, Cox D, Naylor S, Killery A . Structure and variability of human chromosome ends. Mol Cell Biol. 1990; 10(2):518-27. PMC: 360828. DOI: 10.1128/mcb.10.2.518-527.1990. View

20.

Harley C, Futcher A, Greider C . Telomeres shorten during ageing of human fibroblasts. Nature. 1990; 345(6274):458-60. DOI: 10.1038/345458a0. View