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shorten and the cells senesce. If such culturedcells are made to express excessive amounts ofnormal telomerase, the telomeres elongate andovercome cellular senescence, so the cells con-tinue to multiply.

Telomerase is actually a complex of mol-ecules, and its DNA-synthesis function requiresa collaboration between two core components,a protein subunit called TERT and an RNAcomponent called TERC in mice. To explorethe function of TERT, Sarin and colleaguesmade a mouse strain that contained an extraTERT gene; the original TERT gene was leftintact. The extra gene had a control element sothat it could be turned on or off at will in thelive animal. When switched on, the gene pro-duced large amounts of TERT protein in allcells of the animal’s body.

The authors found that when TERT wasoverexpressed in this way the mice were veryfurry, and that this was due to increased prolif-eration of hair-follicle stem cells. A similareffect was independently reported recently for TERT overexpressed only in mouse skin4.These stem cells produce the mature folliclesfrom which hair grows, and the extent of theirproliferation controls fur growth. The authorsnext timed the TERT overexpression to occurat specific periods in the cycling of the hair follicles between their active (anagen) andresting (telogen) stages. They found that the

The way in which a biological entity is firstidentified can limit perceptions of the fullrange of its functions. The telomerase enzyme,for instance, was originally discovered on thebasis of its vital ability to lengthen telomeres —the stretches of non-coding DNA at the endsof chromosomes. If it is too short, a telomereloses the ability to maintain a protective struc-ture at the end of the chromosome, and suchshortened telomeres can signal to cells to ceasemultiplying, in a process called cellular sene-scence. In this issue, Sarin et al. (page 1048)1

report provocative evidence that telomerasedoes more than merely synthesize DNA atchromosome ends: a key subunit of theenzyme stimulates the proliferation of mousehair-follicle stem cells, generating shaggymice. Strikingly, this occurs independently ofthe DNA-synthesis capacity of telomerase.

Telomerase adds DNA to the tips of thechromosomes to replenish the telomeres. This DNA would otherwise dwindle away ascells multiply, owing to incomplete replication of the chromosomal DNA and to enzymesnibbling away at the DNA end regions. In normal human cells, telomerase is highly regu-lated, and its efficiency depends, among otherthings, on the cell type2. The enzyme is presentin very low amounts in most cultured humanprimary cells (that is, those grown directlyfrom biopsies)3, so their telomeres gradually

CELL BIOLOGY

Shaggy mouse talesElizabeth H. Blackburn

First impressions can be misleading. The enzyme telomerase has been wellstudied because of its initial association with cell ageing processes andcancer — but it now seems that this is not all it can do.

The product 14CO2 is, of course, well known in the environmental sciences: following itsuptake by plants and subsequent entry into thefood chain, its radioactive decay provides thebasis for radiocarbon dating.

Manning and colleagues have analysed 13years of 14CO measurements at Baring Head,New Zealand, together with similar data fromAntarctica and ship cruises. After correctingthe time series for the large modulation of 14Cproduction caused by the 11-year solar cycle,residual variations in 14CO remain. As theauthors argue, two instances of higher 14COcan only have been caused by short-termreductions in OH, and the coincidence withknown atmospheric changes confirms theirhypothesis. Their work clearly shows one ofthe advantages of using 14CO for tracking OH.Because of its short lifetime, 14CO is sensitiveto rapid atmospheric changes such as thosethat occur after major volcanic eruptions orlarge-scale episodes of biomass burningrelated to El Niño climatic events. It is alsonotable that the short lifetime of 14CO enabledthe authors to consider the remote SouthernHemisphere as a fairly self-contained atmos-pheric ‘laboratory’ for testing its use.

Figure 1 | Production of 14C, and the OHconnection. Cosmic rays (mainly protons) arescattered and decelerated by the solar-windplasma. But some retain enough energy topenetrate the geomagnetic field and enter Earth’satmosphere as showers of cosmic rays. Nearly allof the neutrons (n) produced in this process arecaptured by nitrogen nuclei, which lose a protonand form atoms of excited radiocarbon, 14C*,which then mainly react to form 14CO. Thesubsequent oxidation of 14CO by OH radicals to 14CO2 is the key reaction that allows Manningand colleagues’ measurements1 of 14CO to be usedin estimating variations of OH concentrations in the atmosphere. This cosmogenic sourceaccounts for about 75% of the 14CO in theatmosphere. The remainder is recycled from the biosphere by biomass burning and oxidationof volatile organic carbons.

Computer models of atmospheric transportand chemistry can generate a fairly detailedpicture of OH distribution. Typically, the max-imum values occur in the tropics, as might beexpected: it is here that atmospheric chemistryis at its most active because of the intense solarradiation and high amounts of water vapour.Verifying the model picture is another matter,and a previous approach that has been repeat-edly applied is based on methyl chloroform,which also offers an indirect way of estimatingOH levels. Careful measurement of this chlorinated industrial chemical at several locations, and calculation of emissions frommanufacturers’ data, have shown that OH has apparently undergone surprisingly largechanges over the past decades4. Yet this andrelated findings have been controversial5,6

because of uncertainties about the actual ratesof emissions. Moreover, the production ofmethyl chloroform has been phased out, and— thanks to OH — it is disappearing from the

atmosphere. So this is not a tracer that can beused in the long term.

By contrast, 14CO is produced naturally andlargely independently of human activity. Itshould become the principal diagnostic toolfor monitoring the oxidative capacity of theatmosphere now and in decades to come. Thistracer is a cosmic dowry for atmosphericchemists — Manning et al. have made a strongcase for them to accept it with gratitude. ■

Patrick Jöckel and Carl A. M. Brenninkmeijer arein the Department of Atmospheric Chemistry,Max Planck Institute for Chemistry, PO Box 3060,55020 Mainz, Germany.e-mail: joeckel@mpch-mainz.mpg.de

1. Manning, M. R., Lowe, D. C., Moss, R. C., Bodeker, G. E. &Allan, W. Nature 436, 1001–1004 (2005).

2. Levy, H. Science 173, 141–143 (1971).3. Weinstock, B. Science 166, 224–225 (1969).4. Prinn, R. G. et al. Science 292, 1882–1888 (2001).5. Spivakovsky, C. M. J. Geophys. Res. 96, 17395–17398 (1991).6. Krol, M. & Lelieveld, J. J. Geophys. Res. 108,

10.1029/2002JD002423 (2003).

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So perhaps TERT forms other complexes withas-yet-unidentified partners.

In ancient Egypt, men smeared their pateswith hippopotamus fat in a desperate bid tostave off baldness12. Is telomerase the new hip-popotamus fat? Probably not. But this enzymeis already known to be vital in sustaining tissues in health and disease, and we shouldlook beyond its eponymous function to under-stand the full spectrum of its potential roles. ■

Elizabeth H. Blackburn is in the Department ofBiochemistry, University of California, SanFrancisco, 600 16th Street, San Francisco,California 94143-2200, USA.e-mail: telomer@itsa.ucsf.edu

1. Sarin, K. Y. et al. Nature 436, 1048–1052 (2005).2. Epel, E. S. et al. Proc. Natl Acad. Sci. USA 101, 17312–17315

(2004).3. Masutomi, K. et al. Proc. Natl Acad. Sci. USA 102,

8222–8227 (2005).4. Flores, I., Cayuela, M. L. & Blasco, M. A. Science advance

online publication 21 July 2005(doi:10.1126/science.1115025).

5. Blackburn, E. H. Nature 408, 53–56 (2000).6. Smith, L. L., Coller, H. A. & Roberts, J. M. Nature Cell Biol. 5,

474–479 (2003).7. Kim, M. M. et al. Proc. Natl Acad. Sci. USA 98, 7982–7987

(2001).8. Li, S., Crothers, J., Haqq, C. M. & Blackburn, E. H. J. Biol.

Chem. 280, 23709–23717 (2005).9. Nosrati, M. et al. Clin. Cancer Res. 10, 4983–4990 (2004).10. Stewart, S. A. et al. Proc. Natl Acad. Sci. USA 99,

12606–12611 (2002).11. Lin, J. & Blackburn, E. H. Genes Dev. 18, 387–396 (2004).12. Ebers papyrus ca. 1550 BC Univ. Leipzig, Spec.

Collections Dept.

overexpressed TERT could reawaken telogenhair follicles, causing them to move into theanagen phase and promoting hair growth.Most remarkably, the prolific hair growth was apparent even when the TERT gene wasoverexpressed in a mouse strain that lackedthe RNA component of telomerase (Fig. 1),showing that the effects on hair growth areindependent of the DNA-synthesis function.

How might the core-protein subunit oftelomerase make mice shaggy in the completeabsence of its function of telomeric DNA synthesis? The answer is unclear. Evidencethat telomerase has additional biological rolesbegan to surface in the late 1990s, throughexperiments on the enzyme in yeast andhuman cells5. Certain partially active mutantforms of telomerase were found to overcomecellular senescence despite massive shorteningof the telomeres; the cells continued to multi-ply even though their telomeres were shorterthan those normally seen in senescent cells5. Inaddition, overexpressing normal telomerase in cultured human primary cells changed thepatterns of gene expression across the wholegenome, whereas cell growth rates and overalltelomere length did not change noticeably6.Moreover, reducing even the small amount of functional telomerase in normal humanfibroblasts (connective-tissue cells) acceleratestheir senescence7. Even before their telomeresshorten, this quickly compromises normalprotective cellular responses to agents thatdamage DNA3.

Human cancer cells commonly have hightelomerase activity, although their telomeresare typically short. However, blocking telom-erase production rapidly inhibits cancer-cellgrowth without telomere shortening, andalters the cells’ gene-expression profile in a distinctive fashion that may be associated with diminished cancer progression8. Indeed,an in vivo model of skin cancer showed thatinhibiting production of the telomerase RNA reduced metastasis9. Although certaincells lacking telomerase can maintain theirtelomeres by an alternative mechanism,

which is independent of telomerase, thetumour-generating capacity of such cells is less than that of cells expressing telomerase10. Conversely, overexpressing TERT in mice promotes early progression of skin cancer4.

How all these effects are mediated, andwhether or how they involve telomerase activ-ity on or off the telomere, are unknown. TERTis known to form at least one complex withouttelomerase RNA — yeast TERT binds to a pro-tein called PinX1 in a manner that is mutuallyexclusive of its binding to telomerase RNA11.

Figure 1 | Telomerase is more than itseemed. The telomerase enzymewas first discovered based on itsability to add DNA to the telomereregions at the ends of chromosomes.It works as a complex with two corecomponents: the protein TERT andan RNA component called TERC in mice. However, Sarin et al.1 findthat TERT can also stimulate theproliferation of hair-follicle stemcells and hair growth — even in the absence of TERC. Perhaps other functions of telomerase have yet to be found.

classes originate was unknown until a distancescale was established, at first on a statisticalbasis5 by comparing the directions of GRBswith models of their possible distribution in theGalaxy. This was followed by direct determina-tion through the discovery of X-ray afterglows6

and the measurement of redshifts through opti-cal line spectroscopy7. Separate models for theorigins of short and long GRBs also emerged.Short GRBs are believed to be associated withthe merger of compact binaries: a pair of neu-tron stars, for example. This explanation is notyet certain, and the Swift mission is designed toclarify the nature of the short bursts.

For long GRBs, the favoured ‘collapsar’model8 starts from the idea of a rapidly rotat-ing, massive star that has undergone extremegravitational collapse and formed a centralblack hole. Complex processes extract some ofthe gravitational binding energy from the diskof material that forms around this black hole;

ASTROPHYSICS

Swift progressDieter H. Hartmann

The agile, choreographed response of the Swift satellite to �-ray burststests models to an unprecedented degree. Results from two recent longbursts suggest that the models are good, but require some tweaking.

The Swift satellite1 is NASA’s latest tool forinvestigating the mysterious phenomenon of �-ray bursts, or GRBs. These intense bursts ofhigh-frequency �-ray and X-ray radiation werediscovered four decades ago2; since Swift’slaunch in November 2004, one such burst hasactivated its detectors every few days. On page985 of this issue, Tagliaferri et al.3 present obser-vations from Swift that suggest strongly that the‘prompt’ emission of the burst and its so-calledafterglow are separate radiation components.This is consistent with models in which theprompt phase of �-radiation, lasting a few to afew hundred seconds, results from internalshocks within the medium that produces them,whereas the longer-lasting afterglow, at lowerfrequencies, is the outcome of interactionsbetween ejected and surrounding material.

The durations of GRBs, together with theirspectral properties, suggest a classification intoshort and long bursts4. How far away both

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