Two Survivor Pathways That Allow Growth in the Absence of Telomerase Are Generated by Distinct Telomere Recombination Events

Chen, Qijun; IJpma, Arne; Greider, Carol W.

doi:10.1128/mcb.21.5.1819-1827.2001

Cited by 252 publications

(307 citation statements)

References 29 publications

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“…Both rad50 7 tlc1 7 and rad51 7 tlc1 7 strains gave rise to survivors, but a triply mutant rad50 7 rad51 7 tlc1 7 strain was as defective as a rad52 7 tlc1 7 strain at generating post-senescent survivors. These two pathways correlated with the two classes of survivors recovered from S. cerevisiae: type I survivors required RAD51 function whereas type II survivors were dependent on RAD50 function (Teng et al, 2000;Chen et al, 2001). However, the correlation between recombination pathway and survivor class may not be absolute, as type II survivors could form in a rad50 7 mutant background, at least at low frequency, but could not be stably maintained (Chen et al, 2001).…”

Section: A Summary Of Potential Molecular Mechanismsmentioning

confidence: 99%

“…These two pathways correlated with the two classes of survivors recovered from S. cerevisiae: type I survivors required RAD51 function whereas type II survivors were dependent on RAD50 function (Teng et al, 2000;Chen et al, 2001). However, the correlation between recombination pathway and survivor class may not be absolute, as type II survivors could form in a rad50 7 mutant background, at least at low frequency, but could not be stably maintained (Chen et al, 2001). Additional analysis has shown that other members of the RAD51 epistasis group (RAD54, RAD55 and RAD57) were also required for the appearance of type I survivors (Le et al, 1999;Chen et al, 2001).…”

Section: A Summary Of Potential Molecular Mechanismsmentioning

confidence: 99%

“…However, the correlation between recombination pathway and survivor class may not be absolute, as type II survivors could form in a rad50 7 mutant background, at least at low frequency, but could not be stably maintained (Chen et al, 2001). Additional analysis has shown that other members of the RAD51 epistasis group (RAD54, RAD55 and RAD57) were also required for the appearance of type I survivors (Le et al, 1999;Chen et al, 2001). Based both on information about genetic requirements and observations of the structural alterations that occur at telomeres, four general models have been proposed for how recombination can maintain telomeres.…”

Section: A Summary Of Potential Molecular Mechanismsmentioning

confidence: 99%

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Telomere maintenance without telomerase

2002

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Recombination-dependent maintenance of telomeres, ®rst discovered in budding yeast, has revealed an alternative pathway for telomere maintenance that does not require the enzyme telomerase. Experiments conducted in two budding yeasts, S. cerevisiae and K. lactis, have shown recombination can replenish terminal G-rich telomeric tracts that would otherwise shorten in the absence of telomerase, as well as disperse and amplify sub-telomeric repeat elements. Investigation of the genetic requirements for this process have revealed that at least two di erent recombination pathways, de®ned by RAD50 and RAD51, can promote telomere maintenance. Although critically short telomeres are very recombinogenic, recombination among telomeres that have only partially shortened in the absence of telomerase can also contribute to telomerase-independent survival. These observations provide new insights into the mechanism(s) by which recombination can restore telomere function in yeast, and suggest future experiments for the investigation of potentially similar pathways in human cells.

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Section: A Summary Of Potential Molecular Mechanismsmentioning

confidence: 99%

Section: A Summary Of Potential Molecular Mechanismsmentioning

confidence: 99%

Section: A Summary Of Potential Molecular Mechanismsmentioning

confidence: 99%

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Telomere maintenance without telomerase

2002

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“…These survivors can be distinguished into type I and type II based on their telomere structure. Type I survivors have short telomeres that are maintained by recombination in the telomere-associated Y 0 element, while type II survivors have very long and heterogeneous telomeres that are likely maintained by intertelomeric recombination (Teng and Zakian, 1999;Teng et al, 2000;Chen et al, 2001). Human ALT cells are reminiscent of type II survivors in yeast (Lundblad and Blackburn, 1993;Bryan et al, 1995Bryan et al, , 1997aTeng and Zakian, 1999).…”

Section: C3-cl6 Cells Do Not Have Subtelomeric Amplificationmentioning

confidence: 99%

A human cell line that maintains telomeres in the absence of telomerase and of key markers of ALT

et al. 2005

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In human somatic cells proliferation results in telomere shortening due to the end replication problem and the absence of adequate levels of telomerase activity. The progressive loss of telomeric DNA has been associated with replicative senescence. Maintenance of telomere structure and function is, therefore, an essential requisite for cells that proliferate indefinitely. Human cells that have acquired the immortal phenotype mostly rely on telomerase to compensate for telomere shortening with cell division. However, a certain percentage of immortalized cell lines and human tumors maintain their telomeres by Alternative Lengthening of Telomeres (ALT), a mechanism not fully understood but apparently based on homologous recombination. Here, we report the isolation of an immortal human cell line that is derived from an ALT cell line but maintains telomeres in the absence of key features of ALT and of telomerase. The properties of these cells suggest that the identification of ALT cells may not be reliably based on known ALT markers. This finding is of relevance for discriminating between the mortal and immortal phenotype among telomerase-negative cells in vitro and in vivo, particularly in regard to the development of pharmacological approaches for cancer treatment based on telomerase inhibition.

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“…Lond. B (2002) of Werner's (WRN) and Bloom's (BLM) syndromes (Huang et al 2001;Chen et al 2001;Le et al 1999).…”

Section: Phil Trans R Soc Lond B (2002)mentioning

confidence: 99%

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology

Fajkus

Šimíčková

Maláska

2002

Phil. Trans. R. Soc. Lond. B

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The past decade has witnessed an explosion of knowledge concerning the structure and function of chromosome terminal structures-telomeres. Today's telomere research has advanced from a pure descriptive approach of DNA and protein components to an elementary understanding of telomere metabolism, and now to promising applications in medicine. These applications include 'passive' ones, among which the use of analysis of telomeres and telomerase (a cellular reverse transcriptase that synthesizes telomeres) for cancer diagnostics is the best known. The 'active' applications involve targeted downregulation or upregulation of telomere synthesis, either to mortalize immortal cancer cells, or to rejuvenate mortal somatic cells and tissues for cellular transplantations, respectively. This article reviews the basic data on structure and function of human telomeres and telomerase, as well as both passive and active applications of human telomere biology.

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Two Survivor Pathways That Allow Growth in the Absence of Telomerase Are Generated by Distinct Telomere Recombination Events

Cited by 252 publications

References 29 publications

Telomere maintenance without telomerase

Telomere maintenance without telomerase

A human cell line that maintains telomeres in the absence of telomerase and of key markers of ALT

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology

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