Telomeres in the mouse have large inter-chromosomal variations in the number of T
            <sub>2</sub>
            AG
            <sub>3</sub>
             repeats

Zijlmans, J. M. J. M.; Martens, Uwe M.; Poon, Steven S.S.; Raap, Anton K.; Tanke, Hans J.; Ward, Rabab K.; Lansdorp, Peter M.

doi:10.1073/pnas.94.14.7423

Cited by 451 publications

(373 citation statements)

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“…Telomerase knockout mouse exhibit decreases fertility, reduced litter size in subsequent generations and eventual sterility [9]. Hetrogenetiy of mouse and human somatic cell telomere length is also seen in oocytes [47]. Other possible mechanisms such as loss of telomerase activity due to mutation in the gene cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Thilagavathi

Mishra

Kumar

et al. 2013

J Assist Reprod Genet

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Purpose Telomere length plays a significant role in various disorders; however, its role in idiopathic recurrent pregnancy loss (iRPL) is not known. The objective of this study was to assess telomere length in peripheral blood leukocytes in couples experiencing unexplained recurrent pregnancy loss (iRPL). Methods The study included 25 couples experiencing iRPL and 20 controls. The mean relative telomere length was measured by quantitative Real Time PCR (Q-PCR) based assay, which measures the average ratio of telomere repeat copy number to a single copy gene (36B4) copy number (T/S ratio) in each sample. Results The relative leukocyte mean telomere length (T/S) in both men and women from iRPL group was significantly lower (p<0.05) when compared to controls. A significant (P<0.05) negative correlation was found between age and leukocyte telomere length (T/S ratio). Among the sperm parameters seminal volume was found to be negatively (r = −0.4679) associated with the telomere T/S ratio. The DNA fragmentation index of sperm showed positive correlation (r=0.4744) with telomere length. In this preliminary study, we found that shorter telomere length in both men and women may be associated with early pregnancy loss. Conclusion In conclusion, shorter telomere length in both male and female partners appears to play a role in the idiopathic recurrent pregnancy loss. Loss of telomeric DNA due to oxidative stress needs further analysis. Analysis of telomere length in germ cells are needed to further substantiate the findings of this study.

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Section: Discussionmentioning

confidence: 99%

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Thilagavathi

Mishra

Kumar

et al. 2013

J Assist Reprod Genet

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“…To demonstrate colocalization of GFP-tagged proteins with telomeric DNA, we analyzed HeLa cells transiently expressing CFP-POT1 and YFP-TRF2 with subsequent fluorescence in situ hybridization by using a Cy3-coupled PNA probe for telomeric DNA (39). These studies clearly demonstrate colocalization of tagged hPOT1 and TRF2 proteins with telomeric DNA (Fig.…”

Section: Characterization Of Cell Lines Expressing Gfp-trf1 Gfp-trf2mentioning

confidence: 99%

“…Immunofluorescence images were obtained by using a Leica DMRXA microscope equipped with a Sensys charge-coupled device camera (Photometrics) and QFluoro software (Leica). To demonstrate colocalization of GFPtagged proteins with telomeric DNA fluorescence in situ hybridization with a Cy3-coupled PNA probe for telomeric DNA was performed (39). For each GFP fusion protein, three independent clones with relatively low GFP fusion protein expression level were selected for bleaching experiments.…”

Section: Methodsmentioning

confidence: 99%

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Dynamics of Protein Binding to Telomeres in Living Cells: Implications for Telomere Structure and Function

Mattern¹,

Swiggers²,

Nigg

et al. 2004

Molecular and Cellular Biology

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Telomeric proteins have an essential role in the regulation of the length of the telomeric DNA tract and in protection against end-to-end chromosome fusion. Telomere organization and how individual proteins are involved in different telomere functions in living cells is largely unknown. By using green fluorescent protein tagging and photobleaching, we investigated in vivo interactions of human telomeric DNA-binding proteins with telomeric DNA. Our results show that telomeric proteins interact with telomeres in a complex dynamic fashion: TRF2, which has a dual role in chromosome end protection and telomere length homeostasis, resides at telomeres in two distinct pools. One fraction (ϳ73%) has binding dynamics similar to TRF1 (residence time of ϳ44 s). Interestingly, the other fraction of TRF2 binds with similar dynamics as the putative end-protecting factor hPOT1 (residence time of ϳ11 min). Our data support a dynamic model of telomeres in which chromosome end-protection and telomere length homeostasis are governed by differential binding of telomeric proteins to telomeric DNA.

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“…Telomere fluorescence was expressed as numbers of molecules of equivalent soluble fluorochrome. Quantitative fluorescence in situ hybridization (Q-FISH) of activated splenocytes and MEFs was performed as described previously (14,78). A Cy3-labeled (CCCTAA) 3 peptide nucleic acid (Applied Biosystems) was used as a probe.…”

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confidence: 99%

Murine Pif1 Interacts with Telomerase and Is Dispensable for Telomere Function In Vivo

Snow

Mateyak

Paderova

et al. 2007

Molecular and Cellular Biology

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Pif1 is a 5 -to-3 DNA helicase critical to DNA replication and telomere length maintenance in the budding yeast Saccharomyces cerevisiae. ScPif1 is a negative regulator of telomeric repeat synthesis by telomerase, and recombinant ScPif1 promotes the dissociation of the telomerase RNA template from telomeric DNA in vitro. In order to dissect the role of mPif1 in mammals, we cloned and disrupted the mPif1 gene. In wild-type animals, mPif1 expression was detected only in embryonic and hematopoietic lineages. mPif1 ؊/؊ mice were viable at expected frequencies, displayed no visible abnormalities, and showed no reproducible alteration in telomere length in two different null backgrounds, even after several generations. Spectral karyotyping of mPif1 ؊/؊ fibroblasts and splenocytes revealed no significant change in chromosomal rearrangements. Furthermore, induction of apoptosis or DNA damage revealed no differences in cell viability compared to what was found for wild-type fibroblasts and splenocytes. Despite a novel association of mPif1 with telomerase, mPif1 did not affect the elongation activity of telomerase in vitro. Thus, in contrast to what occurs with ScPif1, murine telomere homeostasis or genetic stability does not depend on mPif1, perhaps due to fundamental differences in the regulation of telomerase and/or telomere length between mice and yeast or due to genetic redundancy with other DNA helicases.Homeostatic telomere length is achieved by a balance between the extension of the 3Ј telomeric repeats by telomerase or by homologous recombination between telomeric tracts and telomere erosion due to incomplete DNA replication or nucleolytic degradation (30). Telomerase acts to lengthen telomeres via the reverse transcription of an RNA template (encoded by TERC in mammals or TLC1 in Saccharomyces cerevisiae) by a telomerase reverse transcriptase (TERT or Est2, respectively) (30). In the absence of telomerase, telomeric repeats can also be maintained via homologous recombination (12). Excessive telomere lengthening is usually curtailed by cis-inhibitory telomere binding factors, such as Rif1 and Rap1 in S. cerevisiae and TRF1 in humans, or by the action of nucleases (30). In particular instances, telomeric tracts undergo saltatory attrition via the excision of telomeric DNA circles, thus preventing unregulated telomere lengthening (12,40,73).This equilibrium is not simply a push and pull between factors that strictly promote or oppose telomere extension. In S. cerevisiae, the trimeric protein complex composed of Cdc13, Stn1, and Ten1 plays a critical role in the protection of chromosome ends from nucleolytic degradation, and the complex serves both positive and negative roles in the access of telomerase to the telomere during late S phase (24,27,66). The Ku70/Ku80 heterodimer, while essential for nonhomologous end joining, also plays a key role both in the recruitment of telomerase to the telomere and in the protection of ends from degradation (9,25,65,74). Several DNA helicases and nucleases are also known to play ...

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Telomeres in the mouse have large inter-chromosomal variations in the number of T ₂ AG ₃ repeats

Cited by 451 publications

References 35 publications

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Dynamics of Protein Binding to Telomeres in Living Cells: Implications for Telomere Structure and Function

Murine Pif1 Interacts with Telomerase and Is Dispensable for Telomere Function In Vivo

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Telomeres in the mouse have large inter-chromosomal variations in the number of T 2 AG 3 repeats

Cited by 451 publications

References 35 publications

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Analysis of telomere length in couples experiencing idiopathic recurrent pregnancy loss

Dynamics of Protein Binding to Telomeres in Living Cells: Implications for Telomere Structure and Function

Murine Pif1 Interacts with Telomerase and Is Dispensable for Telomere Function In Vivo

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Telomeres in the mouse have large inter-chromosomal variations in the number of T ₂ AG ₃ repeats