Under these conditions,no permanent strat-ification would have been possible, and rela-tively warm, deep water would have formedin most high-latitude regions. As Earthcooled through the Tertiary, however, itreached a threshold coinciding with theonset of glaciation in the Northern Hemi-sphere. In this situation, high-latitude surface waters became so cold that furthercooling in winter did not have enough of aneffect on seawater density to overcome thesalinity gradients. Surface water would thenhave been able to accumulate more freshwater by precipitation, exacerbating stratifi-cation, which would have then become per-manent,as in the modern North Pacific.

Global cooling would then be an impor-tant factor promoting high-latitude stratifi-cation. This, in turn, would have trappedmore carbon from the atmosphere in thedeep sea, thereby lowering greenhousewarming and further intensifying cooling.During the Quaternary climatic cycles thatfollowed, interglacial periods would havebeen sufficiently warm to allow deep winterconvection in the Antarctic Ocean,but not inthe North Pacific.Presumably,during glacialperiods, stratification would also have takenplace in the Antarctic6, thereby contributingto further lowering of atmospheric CO2.

A corollary pertinent to present-day con-cerns is that anthropogenic warming of the

ocean would increase vertical mixing at highlatitudes, thereby further increasing atmos-pheric CO2 and global change. Although itwould take about 1,000 years to fully takeeffect, this would be a totally uncool legacyfor our descendants.

Sigman et al.2 present compelling evi-dence for increased high-latitude stratifica-tion starting 2.7 million years ago. No doubttheir conclusions will stimulate furtherscrutiny of the history of deep-water tem-perature7, and of the validity of their interpretation of the sedimentary record.Nonetheless, they propose an elegantly sim-ple mechanism that could very well explainsome of the major climatic shifts of the geo-logical past. It is refreshing to see that, even in a field as complex as palaeoclimatology,there are still such kernels of simplicity thatmay be ready for the picking. ■

Roger Francois is in the Department of MarineChemistry and Geochemistry, Woods HoleOceanographic Institution, Woods Hole,Massachusetts 02543, USA.e-mail: rfrancois@whoi.edu

1. Zachos, J. et al. Science 292, 686–693 (2001).

2. Sigman, D. M., Jaccard, S. L. & Haug, G. H. Nature 428, 59–63

(2004).

3. Pearson, P. N. & Palmer, M. R. Nature 406, 695–699 (2000).

4. Petit, J. R. et al. Nature 429, 429–436 (1999).

5. Sarmiento, J. L. & Toggweiler, J. R. Nature 308, 621–624 (1984).

6. Haug, G. H. et al. Nature 401, 779–782 (1999).

7. Lear, C. H. et al. Earth Planet. Sci. Lett. 210, 425–436 (2003).

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32 NATURE | VOL 428 | 4 MARCH 2004 | www.nature.com/nature

A t the beginning of mitosis, theprocess of cell division, chromo-somes are organized randomly —

like jigsaw puzzle pieces spread out on thefloor. Their constituent two ‘sister chro-matids’, each of which contains one of thetwo identical DNA molecules produced byreplication, must be oriented such that theywill be pulled in opposite directions intothe two newly forming cells. Like a jigsaw,the solution for correctly orienting all chro-mosomes comes partly through trial anderror. Mechanisms must exist to eliminatewrong configurations while selecting theright ones. The nature of such mechanismswas first suggested by micromanipulationexperiments begun more than 30 yearsago1. Recent molecular analyses in buddingyeast, including a new paper from Dewar et al. on page 93 of this issue2, extend thisearlier work by showing that mechanicaltension is crucial to solving the chromo-some orientation puzzle.

To segregate chromosomes, eukaryoticcells assemble spindles, bipolar arrays ofmicrotubule polymers formed from the pro-tein tubulin. Spindle microtubules attach toa single site on each chromatid where a largemulti-protein complex, the kinetochore, isformed3.When mitosis begins,microtubulesstart a ‘search and capture’ process to findthese kinetochores. This process is random,so some kinetochores fail to attach efficientlyto spindle microtubules. Others generateincorrect attachments — for example,whereboth sister kinetochores attach to the samepole (Fig. 1). Such ‘syntelic’ attachmentsmust be corrected so that all chromosomesare bi-oriented — that is, sister kinetochoresare stably attached to microtubules fromopposite spindle poles. Only then can theglue holding the sister chromatids togetherbe dissolved so that the two spindle poles andtheir associated chromatids are distributedto the daughter cells.

Micromanipulation studies1 first provided

100 YEARS AGOIn his notice of my “Papers on Education,” intaking exception to my nomenclature, Prof.Smithells has touched on a question ofmuch importance to teachers. “Chalk gasseems unnecessary,” he says, “even as atemporary name for carbon dioxide. Why not‘Fixed air,’ which is both descriptive andhistorical?”… “One remark struck me. Hedoes not seem to appreciate that by callingthe gas ‘Fixed air’ you must presuppose thatit is fixed and hence all that the word ‘Fixed’entails of a knowledge of the gas; whereas,your name is eminently descriptive andentails no knowledge of the gas at all butsimply described the source from which itwas first obtained.” Henry E. Armstrong

But I think that history usually supplies a good professional name, such asinflammable air, calx of lead, spirit of nitre…To call carbon dioxide chalk-stuff gasasserts that it comes from chalk, or that, inother words, it is a kind of air fixed somehowin chalk… Historically it was called fixed air,and I value that name because Black’s clearperception and proof that a gas could befixed in a solid and be a weighable part of itwas the means of inspiring Lavoisier withthe right view of the part played by air in thecalcination of metals, and so led to results ofrevolutionary importance. Arthur Smithells

From Nature 3 March 1904.

50 YEARS AGOIn connexion with some recent legalproceedings, a new method for detectingfingerprints has been discovered… Themethod involves the well-known ninhydrintest for amino-acids, often used inchromatography. In this method, fingerprintson paper have always been considered agreat nuisance, and one is oftenrecommended to use forceps “to avoidfingerprints”. In our opinion, the method willbe most suitable for detecting fingerprints onpaper and similar materials… A spontaneousfingerprint contains 98.5–99.5 per centwater, the rest being organic and inorganiccompounds. Normally, the water willevaporate, leaving the rest as a fingerprintpattern containing fats, salts, amino-acids,etc. The last group of substances gives thewell-known reaction with ninhydrin… Fig. 1shows part of a page of a French grammarwhich had not been used for twelve years.The owner’s fingerprint can be comparedwith a fresh print developed on sized paper.From Nature 6 March 1954.

Cell division

Feeling tense enough?Iain M. Cheeseman and Arshad Desai

Accurately distributing half of each replicated chromosome to bothdaughters is a major challenge for dividing cells. The mechanisms usedto achieve this are becoming apparent, thanks to studies old and new.

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evidence that tension between twokinetochores — which is generatedonly in the bi-oriented state (Fig. 1a)— discriminates between bi-orientedand syntelic attachments. However,these studies were conducted on cellsundergoing the first phase of meiosis,the reductive division used to gen-erate gametes. During this phase,two homologous chromosomes,rather than sister chromatids, are connected to opposite spindle poles,so the relevance of this work in mitosiswas unclear. Studies of mitotic chromosomes have shown that sisterkinetochores face in opposite direc-tions regardless of whether they areattached to spindle microtubules4.So when one kinetochore attaches tothe spindle it might geometricallyforce its sister to face the oppositespindle pole and thereby prevent syntely. But recent work demonstra-ting frequent syntelic attachmentsduring mitosis suggests that addi-tional mechanisms also function to ensure bi-orientation. Consistentwith this expectation is the observa-tion that syntelic attachments are corrected by a highly conservedenzyme,Aurora B kinase, in both yeastand vertebrates5,6.

Now, Dewar et al.2 have elegantlymanipulated budding yeast chromo-somes to show that the tension gener-ated in the physical linkage betweenbi-oriented kinetochores and theactivity of Aurora B, rather than anyspecific chromosomal architecture,are sufficient to ensure that the sisterchromatids are appropriately aligned.They reached this striking conclusionin two ways, both of which relied onmicroscopic imaging of fluorescently taggedchromosomes to study their bi-orientationin living cells.

Under normal circumstances, proteincomplexes termed cohesins hold sister chro-matids together until all chromosomes areproperly aligned on the spindle. In the bi-oriented state, microtubules from oppositespindle poles attach to sister kinetochores,and poleward forces act on the kinetochoresto generate tension in the connectionbetween them. Using yeast cells that con-tained defective cohesin and inactive topoisomerase II, an enzyme that resolvesphysically intertwined DNA, Dewar et al.2

showed that sister chromatids with physi-cally linked DNA molecules can efficientlybi-orient without cohesin. A similar findingwas also reported recently in vertebratecells7. So cohesin complexes and the specificconnection they form between sister chro-matids are not required for bi-orientation— a different type of physical connectionwill suffice.

In a technical tour de force, the authorsengineered a circular minichromosome withtwo kinetochores on a single DNA molecule.Remarkably, these artificial minichromo-somes bi-oriented with similar efficiencyand kinetics to those of normal chromo-somes (Fig. 1b). Thus, any physical connec-tion between two kinetochores that supportsthe development of tension can facilitate bi-orientation.

Dewar et al.2 also show that Aurora Bkinase is required to bi-orient the artificialminichromosomes with two kinetochores.Therefore, Aurora B must recognize incor-rect attachments simply by virtue of theirlack of tension, regardless of the precisestructure that links the two kinetochores.Finding out how Aurora B identifies andcorrects them is an obvious next step. Inbudding yeast,where kinetochores assembleon a short (120-base-pair) piece of DNA andbind to just a single microtubule, Aurora Bmust periodically detach kinetochores frommicrotubules until the tense, bi-oriented

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state is achieved. The authors2 providedirect evidence for this by generatingyeast cells that have more than two spindle poles. In such aberrant cells, anengineered minichromosome with justone kinetochore, which can only form asingle attachment and thus lacks tension,moves repeatedly between the differentspindle poles as though it is searching fora stable conformation. If Aurora B func-tion is inhibited, the minichromosomeremains linked to just one spindle pole,indicating that Aurora B detaches micro-tubules from kinetochores in the absenceof tension.

In contrast to budding yeast, kineto-chores of other eukaryotes bind multiplemicrotubules (about 20 in humans)8.These larger kinetochores must coordi-nate all these microtubules and also deal with incorrect attachments inwhich microtubules from opposite spindle poles connect to a single kineto-chore (termed ‘merotely’)9. Anotherstudy10, in this month’s Nature Cell Biology, found that Aurora B does notmerely detach syntelic kinetochoresfrom microtubules in vertebrates — itorchestrates the coordinated disassem-bly of all the microtubules that arebound to each kinetochore, so that thesyntelically oriented chromosomesmove towards the spindle poles beforethey are bi-oriented.

Although sister kinetochore geom-etry seems to be dispensable in buddingyeasts with their single-microtubule-connected kinetochores, it could con-tribute to reducing merotely, as impliedby the conservation of this aspect ofchromosome architecture throughouteukaryotic evolution. Tackling the extradimension that the multiplicity of

microtubule-binding sites at kinetochoresintroduces will undoubtedly be anotherbrain-teaser — and a particularly importantone, too, because the loss of a single chromo-some can be lethal, and aberrant numbers ofchromosomes can contribute to birthdefects and cancer. ■

Iain M. Cheeseman and Arshad Desai are at theLudwig Institute for Cancer Research and theUniversity of California, San Diego, La Jolla,California 92093, USA.e-mails: icheeseman@ucsd.eduabdesai@ucsd.edu1. Nicklas, R. B. & Koch, C. A. J. Cell Biol. 43, 40–50

(1969).

2. Dewar, H., Tanaka, K., Nasmyth, K. & Tanaka, T. U. Nature

428, 93–97 (2004).

3. Cleveland, D. W., Mao, Y. & Sullivan, K. F. Cell 112,

407–421 (2003).

4. Rieder, C. L. Int. Rev. Cytol. 79, 1–58 (1982).

5. Tanaka, T. U. et al. Cell 108, 317–329 (2002).

6. Hauf, S. et al. J. Cell Biol. 161, 281–294 (2003).

7. Vagnarelli, P. et al. EMBO Rep. 5, 167–171 (2004).

8. Bloom, K. Cell 73, 621–624 (1993).

9. Cimini, D. et al. J. Cell Biol. 153, 517–527 (2001).

10.Lampson, M. A., Renduchitala, K., Khodjakov, A. &

Kapoor, T. M. Nature Cell Biol. 6, 232–237 (2004).

Figure 1 Bi-orientation is required for accurate division of sister chromatids. a, Microtubules of the spindle attach to sister chromatids through multi-protein complexes knownas kinetochores. If the microtubules are connected to theopposing spindle poles, the chromosomes are said to be bi-oriented, and tension is generated because the sisterchromatids are held together by a cohesin glue. If, however,the kinetochores of sister chromatids attach to microtubulescoming from the same pole, the chromosomes are said to be syntelic, and no tension is generated. The Aurora B kinase recognizes and corrects the lack of tension in syntelic chromosomes. b, Dewar et al.2 made a circularminichromosome containing two kinetochores and showed that tension could still be generated in the absence of cohesin because the kinetochores were stillphysically connected.

Stable

Tension

Circular minichromosome

b

Bi-oriented(stable)

Syntelic(unstable)

Aurora B

Tension No tensiona

Microtubule

KinetochoreCohesinSister

chromatid

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