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along present-day oceanic spreading centres.But no previous geochemical analysis of theOman mantle rocks has been based on such adetailed field survey as that conducted byLe Me and colleagues. Their high-resolu-tion sampling along the 400 km of theserugged mountains took many months;Figure 1 shows the terrain they had to workin.This exploration geologyapproach,withthe ensuing analytical data firmly anchoredin the context of field geology,is,alas,less andless in vogue in the academic community.

Back in the laboratory,Le Me et al.found

that the chemical composition of Omanmantle rocks varies considerably betweensamples. In particular, incompatible ele-ments show significant variation: simplemass-balance considerations were used tocalculate that the least-depleted samples cor-respond to a relatively low degree of partialmelting (about 10%), whereas the more-depleted samples correspond to partial melt-ing reaching 30%. This range is similar tothat estimated from the composition ofocean-floor basalts2.

Le Me and colleagues most notableresult is related to the geographical distribu-

tion of their data. They show that the varia-tions in composition of Oman mantle rocksare not random but have highs and lows,separated by tens of kilometres,allowing theauthors to define a chemical segmentation ofthis fossil spreading centre. This pattern isreminiscent of those defined on a morpho-logical and geochemical basis along certainsegments of present-day oceanic spreadingcentres. Translated into mantle tempera-tures not, as Ive said, a straightforwardexercise these variations in chemical com-position could correspond to temperaturecontrasts of several tens of degrees, whichare high enough to drive mantle convection.In that respect, Le Me et al. could have

provided the missing link allowing us torelate segmentation of mid-ocean ridges tosmall-scale convection processes in theshallow mantle5.

One possible confounding factor, how-ever, is that a variable degree of partialmelting is not the only way to account forthe variable composition of residual mantlerocks. The shallow mantle may act as a reac-tive filter whose composition, particularly

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NATURE | VOL 432 | 11 NOVEMBER 2004 | www.nature.com/nature 157

in the concentrations of incompatible ele-ments, may be permanently modified bycomplex reactions with magmas percolatingto the surface6. Le Me et al. have made everyeffort to sample areas apparently not affectedby such mantlemelt reactions. But we can-not be entirely sure that they have avoidedthe cryptic effects of these reactions effects that have changed mineral composi-

tion but not mineral proportions.It is often the case that later studies fail to

support this or that scientific model of anatural process, and such could be the fateof Le Me and colleagues interpretation ofchemical variability at spreading centres interms of partial melting. But the map theyhave patiently extracted from the barrendesert rocks of Oman will endure: it willprove an invaluable document in debatesabout basalt composition, mantle processesand the thermal structure of the Earth. Georges Ceuleneer is at the Observatoire

Midi-Pyrnes, CNRS, 14 Avenue E. Belin,

31400 Toulouse, France.e-mail: georges.ceuleneer@cnes.fr

1. Le Me,L., Girardeau, J.& Monnier,C. Nature432, 167172

(2004).

2. Klein,E. M.& Langmuir,C.H.J. Geophys. Res.92, 80898115

(1987).

3. Coleman,R. G.J. Geophys. Res. 86, 24972508 (1981).

4. Allemann,F.& Peters,Tj. Eclogae Geol. Helv. 65, 657697

(1972).

5. Briais, A.& Rabinowicz,M.J. Geophys. Res. 107, ECV-3,117

(2002).

6. Seyler, M.,Toplis,M. J.,Lorand,J.-P.,Luguet,A. & Cannat, M.

Geology29, 155158 (2001).

Adouble-strand break in DNA is thecellular equivalent of a three-alarmfire. As any taxpaying citizen knows,

most communities maintain an impressivecollection of hardware for dealing with

major emergencies. Cells are no different,and for bacteria, the RecBCD complex ofproteins is the heavy machinery that rushesto the scene of the conflagration1. On page187 of this issue, Wigley and colleagues2

unveil the crystal structure ofEscherichia coliRecBCD interacting with a DNA break.Thisremarkable structure helps us to visualizehow the complex careers along the DNA,applies the brakes at a designated site, andchops up unwound DNA in its wake.

RecBCD aids in the repair of double-strand breaks that occur during normal DNAreplication and as a result of damage by ioniz-ing radiation1. It is a tight complex of threeproteins, two of which, RecB and RecD, have

the ability to unwind DNA (they are heli-cases). These two motors move in the samedirection along a DNA double helix, but onopposite strands (hence they move withopposite polarity, RecB progressing in the

so-called 3

to 5

direction, and RecD in the5 to 3 direction). In this way, they can pushtogether against a duplex section of DNA,opening it3,4 (Fig. 1, overleaf). RecB alsochops up the unwound DNA. RecC, mean-while,has been implicated in the recognitionof signal sequences in DNA, known as Chisequences (5-GCTGGTGG-3), that directthe complex to slow down5. Remarkable fea-tures of RecBCD include its unprecedentedspeed and processivity its ability to remainassociated with its substrate together witha puzzling affinity for DNA that is terminatedby a clean cut (a blunt end)1.

The RecBCD structure now published byWigley and colleagues2 reveals an elaborate

DNA repair

Big engine finds small breaksAnna Marie Pyle

When a break occurs in the DNA double helix, it must be dealt withrapidly. The structure of one of the cellular machines responsible isnow revealed, offering insights into its impressive speed and flexibility.

Figure 1 Rough country. The Oman ophiolite, one of the largest outcrops of ocean crust and upper

mantle exposed on the continents, forms a 400-km-long part of the mountains of northern Oman.

G.

CEULENEER

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complex of interlocked proteins that haveinvaded a DNA duplex, opened four basepairs of DNA and sent the separated singlestrands in opposite directions.The 3-termi-nated strand is fed towards the RecB motorand the 5-terminated strand is fed towardsthe RecD motor. RecC appears to managethis operation,holding the helicase domainsof RecB and RecD in place,splitting the DNA

and directing the orientation of the dividedstrands.

The structure is particularly significantbecause it provides a molecular frameworkfor understanding the recognition of ChiDNA by RecC, a protein that has long beenmysterious because it shares little sequencesimilarity with known protein families.Wigley and co-workers show that RecC is noorphan: it has the architecture of an SF1-typehelicase that has lost key catalytic aminoacids. Indeed, the 3-terminated strand ofDNA passes over a region of RecC that istypically used as a helicasenucleic-acid

interface. The structure suggests a remark-able model in which RecC has exchanged theability to actively unwind DNA for the abilityto scan it and then apply the brakes when itpasses over a Chi sequence.

Meanwhile, the structural features ofRecB help to explain why its nucleasedomain occasionally interrupts its continu-ous chewing of the 3-terminated strand ofthe DNA (its exonuclease activity) in order totake a bite out of the other strand (endo-nuclease activity), particularly when thecomplex has paused at a Chi site.RecBs heli-case and nuclease domains are connected by

a long tether that provides sufficient freedomfor the nuclease to take occasional swipes atthe 5-terminated strand.

Although this work provides ampleinsight into the molecular mechanisms forrepairing DNA, it also contains rewards forsimple motorheadssuch as myself who wantto understand how proteins move along,andwork on, DNA and RNA. For example, itgoes a long way towards answering a basicquestion: how can a helicase move so fast?RecBCD unwinds DNA at around 1,000 basepairs per second,which is the fastest machin-ery yet discovered for unwinding nucleic-

acid duplexes. And yet the structure showsthat the RecB and RecD motors look likegeneric SF1 helicases,which typically moseyalong their substrates with comparativelyunexceptional velocities6,7. Indeed,RecB andRecD unwind DNA slowly in isolation.

Although there is probably synergy in thecoupled motion of RecB and RecD, a key tothe speed of the complex may lie with thecomponent that is not a motor: RecC. Bysurrounding and splitting the DNA strandsbefore feeding them to the motors, RecCmight reduce the tendency of the dividedstrands to clamp shut, allowing RecB andRecD to move faster. RecC is also likely toenhance processivity by effectively tying

RecB and RecD to the substrate. Whateverits mechanism of action, RecC clearlyengages the DNA before delivering it to themotors, thereby turbo-charging two other-wise unexceptional engines.

The structure also helps us understandhow a helicase can move backwards. MostSF1 and SF2 helicases move along singlestrands of DNA or RNA in a 3 to 5 manner.However, single-molecule studies havedetected apparent backward motion by heli-cases8, and there are examples of closelyrelated helicases (such as Dda and, of course,RecD) that move in the opposite direc-tion3,4,9. The new structure shows that RecDdoes not do this by turning around that is,the helicase domains are not arranged in anopposite orientation relative to the polarityof the DNA strand. Rather, RecD simplydrives in reverse, much like variants of thecytoskeletal motors myosin and kinesin10.

This structural evidence for forward andreverse gears in a helicase opens the door tostructurefunction studies aimed at under-standing directionality of motion.

Insights into how helicases and substratesrecognize each other are also provided.Mosthelicases require a single-stranded launchpad attached to the duplex before they caninitiate unwinding11. But RecBCD can load

directly onto a DNA blunt end,and the struc-ture shows how: it creates its own single-stranded tails by melting the first four basepairs of the duplex in the absence of adeno-sine triphosphate (ATP, the fuel for biologi-cal motors such as helicases). So the intrinsicbinding energy of the motor makes majorcontributions to unwinding events prior toany conformational changes that areinduced by ATP hydrolysis.

Despite the appealing mechanical con-cepts suggested by the new structure,however,it should be emphasized that it represents asnapshot of an initiation complex that has

not undergone forward motion in the pres-ence of ATP. The actively translocating com-plex may, in fact, contain features that differmarkedly from those seen here.For example,a compelling feature of the complex is thepin provided by RecC that appears to splitthe DNA strands before they are delivered toRecB and RecD. However, the pin substruc-ture may be subjected to substantial forceduring forward motion.It will be interestingto see whether it persists during unwinding,and to understand its mechanical role inRecBCD complexes that are actively moving.

Similarly, it will be essential to explore the

existence of the proposed binding sitebetween RecC and the Chi sequence, and totest the suggested model by which theChiRecC interaction regulates the nucleaseactivity of RecB. Like any significant crystalstructure, that of RecBCD poses intriguingnew questions.In this case, it also provides avaluable roadmap for mutational and mech-anistic analyses. Anna Marie Pyle is in the Department of Molecular

Biophysics and Biochemistry, and the Howard

Hughes Medical Institute, Yale University,

266 Whitney Avenue, New Haven,

Connecticut 06520, USA.

e-mail: anna.pyle@yale.edu1. Kowalczykowski, S.C. Trends Biochem. Sci. 25, 156165 (2000).

2. Singleton,M. R.,Dillingham,M. S.,Gaudier, M.,Kowalczykowski,

S.C. & Wigley,D.B. Nature432, 187193 (2004).

3. Dillingham,M. S.,Spies, M.& Kowalczykowski,S. C. Nature

423, 893897 (2003).

4. Taylor, A.F.& Smith,G. R. Nature423, 889893 (2003).

5. Handa,N., Ohashi, S.,Kusano, K.& Kobayashi,I. Genes Cells2,

525536 (1997).

6. Cheng,W.,Hsieh, J., Brendza,K. M.& Lohman,T.M.

J. Mol. Biol. 310, 327350 (2001).

7. Maluf,N. K.,Fischer, C.J. & Lohman, T. M.J. Mol.Biol. 325,

913935 (2003).

8. Dessinges,M. N.,Lionnet, T.,Xi, X.G., Bensimon,D. &

Croquette,V. Proc.Natl Acad.Sci. USA 101, 64396444 (2004).

9. Raney, K.D.& Benkovic, S.J.J. Biol.Chem. 270, 2223622242

(1995).

10.Vale, R.D. & Milligan,R. A. Science288, 8895 (2000).

11.Delagoutte,E. & von Hippel,P.H. Q. Rev. Biophys. 35, 431478(2002).

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158 NATURE | VOL 432 | 11 NOVEMBER 2004 | www.nature.com/nature

Figure 1 Heavy machinery for dealing with DNA

breaks. The RecBCD complex of proteins helps

to repair DNA by unwinding the DNA double

helix in the region of a double-stranded break,

and chopping up the unwound strands. RecB

and RecD are helicases that push on the DNA

duplex together to unwind it.RecB also has

nuclease activity, which snips up the unwound

DNA. RecC has been implicated in recognizingDNA sequences that direct the complex to slow

down. Wigley and colleagues2 have now

presented the crystal structure of RecBCD

bound to DNA, revealing details such as how the

complex binds DNA at the site of a break and

how the actions of the three proteins are

coordinated.

2004 NaturePublishingGroup