Telomeres, Telomerase and Chromosome Stability

Rj, Preston

doi:10.2307/3579618

Cited by 52 publications

(22 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Telomere capture or telomere healing are well characterized in neoplastic chromosome rearrangements (Meltzer et al, 1993;Melek and Shippen, 1996;Preston, 1997), and are also involved in the reconstitution of telomeres in constitutional terminal chromosome deletions (Flint et al, 1994;Vermeesch et al, 1998;Ballif et al, 2000;Varley et al, 2000). In this communication, we describe a patient with a terminal inversion duplication of 8p, stabilized after telomere capture of a cytogenetically detectable portion of distal 18q.…”

Section: Introductionmentioning

confidence: 94%

Stabilization of a terminal inversion duplication of 8p by telomere capture from 18q

Kostiner

Nguyen

Cox

et al. 2002

Cytogenet Genome Res

View full text Add to dashboard Cite

Terminal inversion duplications of the short arm of chromosome 8 are one of the more common chromosome rearrangements in humans. We report an infant with multiple congenital anomalies, in whom karyotype analysis showed a terminal inversion duplication of 8p including additional material at the distal end of the derivative chromosome, shown to be of chromosome 18q origin. Terminal inversion duplications of 8p are the result of meiotic recombination between inverted olfactory gene receptor repeats in 8p. This recombination generates a dicentric intermediate that breaks during anaphase, and the broken chromosome end is stabilized by telomere healing or telomere capture. The origin of the telomeric region in the majority of constitutional chromosome deletions studied to date was shown to be from telomere healing; the de novo addition of telomeric repeats. In the proband a cytogenetically detectable piece of chromosome 18q was present on the distal end of the derivative 8, suggesting that this chromosome was stabilized by telomere capture of 18q. FISH analyses of additional cases may yield information as to whether telomere capture or telomere-healing events are the predominant mechanism of chromosome stabilization in terminal inversion duplications of 8p.

show abstract

Section: Introductionmentioning

confidence: 94%

Stabilization of a terminal inversion duplication of 8p by telomere capture from 18q

Kostiner

Nguyen

Cox

et al. 2002

Cytogenet Genome Res

View full text Add to dashboard Cite

show abstract

“…Shortly thereafter, McClintock's (2) cytogenetic studies in maize demonstrated that broken chromosomes were subject to end fusions. These studies demonstrated that a cell's ability to respond differently to natural chromosome ends than it does to ends created by spontaneous or induced breakage is critical to preserving a stable genetic inheritance (3)(4)(5). Modern molecular analysis has revealed that telomeric DNA consists of tandem arrays of short, repetitive G-rich (6, 7) sequence oriented 5Ј-to-3Ј toward the end of the chromosome, terminating in a 3Ј singlestranded G-rich overhang (8).…”

mentioning

confidence: 99%

DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes

Bailey

Meyne

Chen

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

364

275

View full text Add to dashboard Cite

Recent findings intriguingly place DNA double-strand break repair proteins at chromosome ends in yeast, where they help maintain normal telomere length and structure. In the present study, an essential telomere function, the ability to cap and thereby protect chromosomes from end-to-end fusions, was assessed in repairdeficient mouse cell lines. By using fluorescence in situ hybridization with a probe to telomeric DNA, spontaneously occurring chromosome aberrations were examined for telomere signal at the points of fusion, a clear indication of impaired end-capping. Telomeric fusions were not observed in any of the repair-proficient controls and occurred only rarely in a p53 null mutant. In striking contrast, chromosomal end fusions that retained telomeric sequence were observed in nontransformed DNA-PKcs-deficient cells, where they were a major source of chromosomal instability. Metacentric chromosomes created by telomeric fusion became even more abundant in these cells after spontaneous immortalization. Restoration of repair proficiency through transfection with a functional cDNA copy of the human DNA-PKcs gene reduced the number of fusions compared with a negative transfection control. Virally transformed cells derived from Ku70 and Ku80 knockout mice also displayed end-to-end fusions. These studies demonstrate that DNA double-strand break repair genes play a dual role in maintaining chromosomal stability in mammalian cells, the known role in repairing incidental DNA damage, as well as a new protective role in telomeric end-capping.

show abstract

“…As telomeric DNA shortens progressively with time due to an end-replication mechanism, dysfunctional telomeres may recombine and fuse, initiating random chromosome breakage, translocations, and the formation of dicentric chromosomes. This process is associated with increasing chromosome instability and the risk of oncogenesis [Counter et al, 1992;Preston, 1997].…”

mentioning

confidence: 99%

Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis

Laish¹,

Mannasse-Green

Hadary³

et al. 2016

Cytogenet Genome Res

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.

show abstract

Telomeres, Telomerase and Chromosome Stability

Cited by 52 publications

References 46 publications

Stabilization of a terminal inversion duplication of 8p by telomere capture from 18q

Stabilization of a terminal inversion duplication of 8p by telomere capture from 18q

DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes

Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis

Contact Info

Product

Resources

About