Telomere associations in interphase nuclei: Possible role in maintenance of interphase chromosome topology

Robert G. Nagele, Antonio Q. Velasco, William J. Andersen, Donald J. McMahon, Zabrina Thomson, Jessica Fazekas, Kelly Wind, Hsin Yi Lee

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


The relative sizes of individual telomeres in cultured human cells under conditions of cell cycling, replicative quiescence, cell transformation and immortalization were determined using quantitative fluorescence in situ hybridization (Q-FISH) with a telomere-specific peptide nucleic acid (PNA) probe. Results obtained from analysis of telomere length profiles (TLPs), which display the distribution of relative telomere lengths for individual cells, confirmed telomere length heterogeneity at the single cell level and proportional shortening of telomere length during replicative aging of virus-transformed cells. TLPs also revealed that some telomeric ends of chromosomes are so closely juxtaposed within interphase nuclei that their fluorescent signals appear as a single spot. These telomeric associations (TAs) were far more prevalent in interphase nuclei of noncycling normal and virus-transformed cells than in their cycling counterparts. The number of interphase TAs per nucleus observed in late-passage E6/E7-transformed cells did not increase during progression to crisis, suggesting that telomere shortening does not increase the frequency of interphase TAs. Furthermore, interphase TAs were rarely observed in rapidly cycling, telomerase-positive, immortalized cells that exhibit somewhat shortened, but stabilized, telomere length through the activity of telomerase. Our overall results suggest that the number of interphase TAs is dependent more on whether or not cells are cycling than on telomere length, with TAs being most prominent in the nuclei of replicatively quiescent cells in which nonrandom (even preferred) chromosome spatial arrangements have been observed. We proposed that interphase TAs may play a role in the generation and/or maintenance of nuclear architecture and chromosome positional stability in interphase nuclei, especially in cells with a prolonged G1/G0 phase and possibly in terminally differentiated cells.

Original languageEnglish (US)
Pages (from-to)377-388
Number of pages12
JournalJournal of cell science
Issue number2
StatePublished - 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology


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