Closed chromatin loops at the ends of chromosomes

Nikitina, Tatiana; Woodcock, Christopher L.

doi:10.1083/jcb.200403118

Cited by 128 publications

(118 citation statements)

References 36 publications

(53 reference statements)

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“…The 't-loop' structure, in which the 3' overhang loops back on the double stranded telomeric DNA and invades the duplex, was inferred by electron microcopy and indirect biochemical experiments [28,48] (Fig. 1).…”

Section: Telomere Structurementioning

confidence: 99%

Cancer and aging: the importance of telomeres in genome maintenance

Rodier

Kim

Nijjar

et al. 2005

The International Journal of Biochemistry & Cell Biology

118

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Telomeres are the specialized DNA-protein structures that cap the ends of linear chromosomes, thereby protecting them from degradation and fusion by cellular DNA repair processes. In vertebrate cells, telomeres consist of several kilobase pairs of DNA having the sequence TTAGGG, a few hundred base pairs of single-stranded DNA at the 3' end of the telomeric DNA tract, and a host of proteins that organize the telomeric double and single stranded DNA into a protective structure.

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Section: Telomere Structurementioning

confidence: 99%

Cancer and aging: the importance of telomeres in genome maintenance

Rodier

Kim

Nijjar

et al. 2005

The International Journal of Biochemistry & Cell Biology

118

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“…In this paper we use a value of L p ¼ 40 nm. Telomere chromatin fibers observed by EM exhibit an irregular diameter that ranges from 10 to 30 nm (29). In our model we choose the diameter as the average of these two values (d ¼ 20 nm).…”

Section: Methodsmentioning

confidence: 99%

Quantitative theory of telomere length regulation and cellular senescence

Rodriguez-Brenes

Peskin

2010

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

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In normal somatic cells, telomere length shortens with each cell replication. This progressive shortening is associated with cellular senescence and apoptosis. Germ cells, stem cells, and the majority of cancer cells express telomerase, an enzyme that extends telomere length and, when expressed at sufficient levels, can immortalize or extend the life span of a cell line. It is believed that telomeres switch between two states: capped and uncapped. The telomere state determines its accessibility to telomerase and also the onset of senescence. One hypothesis is that the t loop, a large lariat-like structure, represents the capped state. In this paper we model a telomere state on the basis of the biophysics of t-loop formation, allowing us to develop a single mathematical model that accounts for two processes: telomere length regulation for telomerase positive cells and cellular senescence in somatic cells. The model predicts the steady-state length distribution for telomerase positive cells, describes the time evolution of telomere length, and computes the life span of a cell line on the basis of the levels of TRF2 and telomerase expression. The model reproduces a wide range of experimental behavior and fits data from immortal cell lines (HeLa S3 and 293T) and somatic cells (human diploid fibroblasts) well. We conclude that the t loop as the capped state is a quantitatively reasonable model of telomere length regulation and cellular senescence. mathematical model | telomerase | telomeres T elomeres are noncoding repetitive sequences of DNA at the end of the chromosomes of eukaryotic cells. They play an important role in "hiding" the end of the chromosomes from the DNA damage response pathway. Dysfunctional telomeres may be interpreted as DNA breaks that may lead to nonhomologous end joining and may trigger senescence or apoptosis through the p53 and p16-RB pathways (1, 2).Because of the linear nature of eukaryotic DNA and the unidirectional synthesis of DNA polymerases, normal human somatic cells are unable to replicate their DNA completely (3). It is also believed that telomeres are actively degraded by an unknown exonuclease (4). These processes together with the action of oxidative stress (5) result in the progressive shortening of telomeres. Both in vivo and in vitro telomere lengths correlate with cellular life span.Germ cells, stem cells, and cancer cells (in approximately 85% of cancer types) express telomerase, an enzyme that extends telomere length (6). Cells that express telomerase at sufficient levels maintain a stable telomere length and have an unlimited replication capacity (7). Furthermore, it has been shown that the introduction of telomerase into normal human cells can extend the life span of a cell culture (8).The function and dynamics of telomeres depend on the action of several proteins that interact with chromosome ends. Particular attention has been given to shelterin, a complex of six telomere-specific proteins that protect and reshape telomeres (9). A key feature of shelterin is its ability...

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“…G-rich overhangs have a central role in sustaining a diverse array of telomeric functions and are thought to invade the preceding duplex region of the telomere to form a lariat-like structure called the t-loop. This higher-order architecture, which was revealed by electron microscopy (Griffith et al, 1999;Nikitina and Woodcock, 2004;Raices et al, 2008), provides one mechanism by which chromosome ends maintain their protective cap.…”

Section: The Composition Of Chromosome Endsmentioning

confidence: 99%

Telomeres at a glance

Sfeir

2012

Journal of Cell Science

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Closed chromatin loops at the ends of chromosomes

Cited by 128 publications

References 36 publications

Cancer and aging: the importance of telomeres in genome maintenance

Cancer and aging: the importance of telomeres in genome maintenance

Quantitative theory of telomere length regulation and cellular senescence

Telomeres at a glance

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