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Journal ArticleDOI

The Behavior in Successive Nuclear Divisions of a Chromosome Broken at Meiosis

01 Aug 1939-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 25, Iss: 8, pp 405-416
TL;DR: After reporting her observations of ring chromosomes, McClintock followed broken chromatids through successive cycles of cell division, in which she could observe the behavior of the "monstrous" chromosome 9 through meiosis and crossing-over, which meant that she could selectively produce persistent variegation in plant tissues.
Abstract: After reporting her observations of ring chromosomes, McClintock followed broken chromatids through successive cycles of cell division, in which she could observe the behavior of the "monstrous" chromosome 9 through meiosis and crossing-over. McClintock reported in a long series of articles that the chromatid breakage-fusion-bridge (BFB) cycle occurred only in the germ cells and endosperm, while the chromosome BFB continued in the sporophyte, which meant that she could selectively produce persistent variegation in plant tissues.
Citations
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Journal ArticleDOI
01 Sep 1995-Science
TL;DR: Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity, and cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings.
Abstract: Eukaryotic chromosomes are capped with repetitive telomere sequences that protect the ends from damage and rearrangements. Telomere repeats are synthesized by telomerase, a ribonucleic acid (RNA)-protein complex. Here, the cloning of the RNA component of human telomerase, termed hTR, is described. The template region of hTR encompasses 11 nucleotides (5'-CUAACCCUAAC) complementary to the human telomere sequence (TTAGGG)n. Germline tissues and tumor cell lines expressed more hTR than normal somatic cells and tissues, which have no detectable telomerase activity. Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity. HeLa cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings. Thus, human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells.

2,305 citations

Journal ArticleDOI
05 Oct 2001-Cell
TL;DR: The data indicate that, while average telomere length is measured in most studies, it is not the average but rather the shortest telomeres that constitute telomerre dysfunction and limit cellular survival in the absence of telomerase.

1,019 citations

Journal ArticleDOI
TL;DR: The crucial role of telomeres in cell turnover and aging is highlighted by patients with 50% of normal telomere levels resulting from a mutation in one of the telomerase genes, implicated in a variety of disorders including dyskeratosis congenita, aplastic anemia, pulmonary fibrosis, and cancer.
Abstract: Telomeres play a central role in cell fate and aging by adjusting the cellular response to stress and growth stimulation on the basis of previous cell divisions and DNA damage. At least a few hundred nucleotides of telomere repeats must "cap" each chromosome end to avoid activation of DNA repair pathways. Repair of critically short or "uncapped" telomeres by telomerase or recombination is limited in most somatic cells and apoptosis or cellular senescence is triggered when too many "uncapped" telomeres accumulate. The chance of the latter increases as the average telomere length decreases. The average telomere length is set and maintained in cells of the germline which typically express high levels of telomerase. In somatic cells, telomere length is very heterogeneous but typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age. Loss of (stem) cells via telomere attrition provides strong selection for abnormal and malignant cells, a process facilitated by the genome instability and aneuploidy triggered by dysfunctional telomeres. The crucial role of telomeres in cell turnover and aging is highlighted by patients with 50% of normal telomerase levels resulting from a mutation in one of the telomerase genes. Short telomeres in such patients are implicated in a variety of disorders including dyskeratosis congenita, aplastic anemia, pulmonary fibrosis, and cancer. Here the role of telomeres and telomerase in human aging and aging-associated diseases is reviewed.

973 citations


Cites background from "The Behavior in Successive Nuclear ..."

  • ...That chromosome ends play an important role in ensuring chromosome stability was first proposed in the 1930s by Barbara McClintock working with maize (142)...

    [...]

Journal ArticleDOI
07 Mar 1997-Cell
TL;DR: Using a primer-extension/nick-translation technique and non-enaturing hybridization, the authors found long 3' G-rich tails at human chromosome ends in mortal primary fibroblasts, umbilical vein endothelial cells, and leukocytes.

901 citations

Journal ArticleDOI
01 Nov 1979-Nature
TL;DR: A yeast DNA sequence that behaves as a chromosomal replicator, ars1 (autonomously replicating sequence), has been isolated and allows autonomous replication of all co-linear DNA.
Abstract: A yeast DNA sequence that behaves as a chromosomal replicator, ars1 (autonomously replicating sequence), has been isolated. On transformation, ars1 allows autonomous replication of all co-linear DNA. The replicator can integrate into other replication units and can function in multimeric form. The 850-base pair ars1 element has no detectable homology to other yeast sequences. Such replicator-containing plasmids can be used for the isolation of DNA sequences in yeast cells as well as for the study of chromosomal DNA replication.

897 citations

References
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Journal ArticleDOI
TL;DR: In this seldom-cited paper, McClintock established the crossover frequencies and order of the genes C (red aleurone in the kernel), Sh (shrunken endosperm), and Wx (waxyendosperm).
Abstract: In this seldom-cited paper, published in the same issue of the "Proceedings of the National Academy of Sciences" as Creighton and McClintock's paper on genetic and cytological crossingover, McClintock established the crossover frequencies and order of the genes C (red aleurone in the kernel), Sh (shrunken endosperm), and Wx (waxy endosperm).

52 citations

Journal ArticleDOI
01 Sep 1934-Genetics
TL;DR: Page 438, Table 4, under Plant Number column, lines 1 in upper and lower halves, for "2434—9" read "2464—9."
Abstract: Page 438, Table 4, under Plant Number column, lines 1 in upper and lower halves, for "2434—9" read "2464—9." Page 438, Table 4, under Plant Number column, line 6 in upper half, delete "2464-4.*" Page 446, line 7, for "pollen or trisomics" read "pollen of trisomics

26 citations