It Field

PERSPECTIVES

*. D. A. Erie, O. Hajiseyedjavadi, M. C. Young, P. H. von

reading is only now emerging, DNA proofread- the stereochemical basis for RNA proofread-

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merases cleave misincorporated nucleotides studies should clarify how back-stepping and 6. H. Kettenberger, K.-J. Armache, P. Cramer, Cell 114, 347

from the growing DNA chain, but the cleavage other rearrangements at the tunable poly- (2003).

activity resides in a protein domain distinct merase active site are triggered. Techniques 7. N. Opalka et al., Cell 114, 335 (2003).

8. V. Sosunov et al., Nucleic Acids Res. 33, 4202 (2005).

from the domain for synthesis (14). The spatial must also be developed to probe the in vivo sig-

9. P. Cramer, D. A. Bushnell, R. D. Kornberg, Science 292,

separation of the two activities probably nificance of different aspects of the transcrip- 1863 (2001).

allowed optimization of two dedicated active tion mechanism discovered in vitro. 10. T. A. Steitz, Nature 391, 231 (1998).

sites during evolution, whereas RNA poly- 11. D. G. Vassylyev et al., Nature 417, 712 (2002).

12. K. D. Westover, D. A. Bushnell, R. D. Kornberg, Cell 119,

merase retained a single tunable active site. References

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This could explain how some DNA poly- 1. N. Zenkin, Y. Yuzenkova, K. Severinov, Science 313, 518

13. A. M. Poole, D. T. Logan, Mol. Biol. Evol. 22, 1444

(2006).

merases achieve very high fidelity, which is (2005).

2. M. Orlova, J. Newlands, A. Das, A. Goldfarb, S. Borukhov,

required for efficient error correction during 14. L. S. Beese, T. A. Steitz, EMBO J. 10, 25 (1991).

Proc. Natl. Acad. Sci. U.S.A. 92, 4596 (1995).

replication of large DNA genomes. 3. M. J. Thomas, A. A. Platas, D. K. Hawley, Cell 93, 627

In the future, structural studies will unravel (1998). 10.1126/science.1131205

PHYSICS

A More Precise The fine structure constant, a vital quantity in

quantum theory, sets the scale for the physical

world. Recent measurements have improved its

Fine Structure Constant precision by a factor of 10.

Daniel Kleppner

elativistic quantum electro- Tomonaga, and Dyson ( 5 ).

R Trap cavity Electron

dynamics (QED) the the- According to QED, the electron

ory that describes electro- g-factor would differ slightly

Top endcap electrode

magnetic interactions between all from 2. Kusch and Foley discov-

electrically charged particles is Quartz spacer ered experimentally that the g-

the most precisely tested theory in factor differed from 2 by about 1

physics. In studies of the magnetic part in a thousand (6). For this

Compensation electrode

moment of the electron (a measure work Kusch received the Nobel

of its intrinsic magnetic strength), Prize in 1955, followed by Sch-

Ring electrode Nickel rings

theory and experiment have been winger, Feynman, and Tomo-

shown to agree within an uncer- naga, who received the Nobel

Compensation electrode

tainty of only 4 parts per trillion. Prize in 1965. In 1987 Dehmelt

This astounding precision has just published the measurement re-

been improved. A new measure- ferred to above, accurate to 4

ment by Odom et al. (1) has in- parts per trillion, for which he

Bottom endcap electrode

creased the experimental precision received the Nobel Prize in 1989

Field emission point

0.5 cm

by a factor close to 6. In a parallel One-electron cyclotron. A magnetic field along the axis confines the electron radi- (7). The major experimental

theoretical effort, Gabrielse et al. ally; an oscillating electric field applied to the endcap electrodes confines it longitu- innovation in Dehmelt s meas-

(2) have extended the QED calcu- dinally. Nickel rings slightly perturb the magnetic field so as to couple the radial and urement was a technique that

lations of the magnetic moment to longitudinal motions. The electron is trapped in a cavity that inhibits spontaneous allowed him to observe a single

a new level of precision. By com- emission. Other electrodes are used to control the electric field so as to reduce QED electron. The experiment of

bining these advances, the preci- effects of the vacuum. Gabrielse and colleagues builds

sion with which we know the value on Dehmelt s work but incorpo-

of the fine structure constant is now 10 times as The quantity that has been measured by these rates major innovations that make the isolated

high as that obtained by any other method. The researchers is the ratio of the magnetic moment electron into a quantum system whose energy

fine structure constant is a dimensionless num- of the electron to the fundamental atomic unit of levels can be probed.

ber, ~1 137, which involves the charge of the magnetism known as the Bohr magneton. This The experiment compares the two types of

CREDIT: G. BABRIELSE/HARVARD UNIVERSITY

electron, the speed of light, and Planck s con- dimensionless ratio is called the g-factor of the motion of an electron in a magnetic field. The

stant. It is usually designated, and it plays a electron. Because the g-factor is a basic property first is circular motion around the direction of

ubiquitous role in quantum theory, setting the of the simplest of the elementary particles, it has the field at a frequency known as the cyclotron

scale for much of the physical world. Thus, played a prominent role both in motivating and frequency fc because the motion is described

occupies an honored position among the fun- testing QED. According to Dirac s theory of the by the same equation as that for charged parti-

damental constants of physics. electron (3, 4), for which he received the Nobel cles in a cyclotron accelerator. The second type

Prize in 1933, the g-factor should be exactly 2. In of motion is spin precession. An electron pos-

the period immediately following World War II, sesses intrinsic spin, somewhat in analogy to

The author is in the Department of Physics, Massachusetts

new data on the spectrum of hydrogen led to the spin of a flywheel in a gyroscope. If a gyro-

Institute of Technology, Cambridge, MA 02139, USA.

the creation of QED by Schwinger, Feynman, scope is suspended by one end of its axle, it

E-mail: abql4t@r.postjobfree.com

448 28 JULY 2006 VOL 313 SCIENCE www.sciencemag.org

Published by AAAS

PERSPECTIVES

experiences a torque due to its weight and pre- term, needed to interpret the new experimental knows where that boundary is for QED. It is

hoped that other measurements of will con-

cesses about a vertical axis. Similarly, in a results, required evaluating 891 Feynman dia-

magnetic field, an electron experiences a grams (9). This task involved numerical inte- tinue to improve so that they can be combined

torque due to its magnetic moment, and the grations on supercomputers over a period of with these new measurements to extend QED s

electron spin axis precesses about the field at a more than 10 years, augmented by delicate ana- area of validity or, better yet, find its boundary.

frequency fs. The g-factor differs from 2 by the lytical calculations that were required to deal Furthermore, there are a number of avenues

ratio (fs fc)/fc. The quantities actually meas- with the infinities that underlie QED. for improving the measurements made by

ured are the cyclotron frequency fc and the dif- If the fine structure constant were known to Gabrielse and his colleagues. The electron s

ference frequency (fs fc ). a precision of 0.7 parts per billion, it could be magnetic moment is now known to better than

To carry out the measurement, Gabrielse inserted in the theoretical formula to provide a a part per trillion, but the ultimate precision is

and co-workers designed a one-electron true test of QED. A discrepancy would be of not yet in sight.

cyclotron in which the underlying quantum major importance because it would be an indi-

nature of the electron s motion is both ex- cation of new physics. A number of different References

experiments have yielded values of, but none 1. B. Odom, D. Hanneke, B. D Urso, G. Gabrielse, Phys. Rev.

ploited and controlled (see the figure). In the

Lett. 97, 030801 (2006).

theory of QED, the vacuum plays an important with the precision required for this test. 2. G. Gabrielse, D. Hanneke, T. Kinoshita, M. Nio, B. Odom,

dynamical role. The radiation field of the vac- Consequently, the theoretical results are most Phys. Rev. Lett. 97, 030802 (2006).

usefully applied to extract a new value of

uum (a fluctuating field in totally empty space) 3. P. A. M. Dirac, Proc. R. Soc. London A 117, 610 (1928).

4. P. A. M. Dirac, Proc. R. Soc. London A 118, 351 (1928).

is a principal source of the electron moment from the experiment. The new value is approx-

5. S. Schweber, Q.E.D. and the Men Who Made It: Dyson,

anomaly. The vacuum field is slightly affected imately 10 times as accurate as previous Feynman, Schwinger, and Tomonaga (Princeton Univ.

by conducting surfaces, such as the electrodes values. For the record, the value (expressed Press, Princeton, NJ, 1994).

in the one-electron cyclotron. By carefully as an inverse value) found by Gabrielse and 6. P. Kusch, H. M. Foley, Phys. Rev. 74, 250 (1948).

Kinoshita and their colleagues is 1 = 7. R. S. Van Dyck Jr., P. B. Schwinberg, H. G. Dehmelt, Phys.

controlling the geometry of the cyclotron,

Rev. Lett. 59, 26 (1987).

Gabrielse and his colleagues essentially elimi- 137.035999710, with an uncertainty of 0.7

8. S. Laporta, E. Remiddi, Phys. Lett. B 379, 283 (1996).

nated perturbation of the g-factor by the vac- parts per billion. 9. T. Kinoshita, M. Nio, Phys. Rev. D 73, 013003 (2006).

uum. Using principles of cavity QED, the Although theories in physics all have

researchers arranged the geometry so as to boundaries to their areas of validity, nobody 10.1126/science.1131834

substantially prevent the orbiting electron from

radiating its energy, thereby lengthening the

observation time of each measurement. CELL SIGNALING

Because cyclotron motion is inherently

Protein Kinases Seek Close

quantized, the energy of a circulating charged

particle can change only in steps of hfc, where

h is Planck s constant. Normally these energy

Encounters with Active Genes

steps are so small compared to the particle s

energy that the underlying quantum nature of

the motion is unimportant. In the quantum John W. Edmunds and Louis C. Mahadevan

one-electron cyclotron, however, the energy

is so finely controlled that each discrete step Signaling kinases may form integral components of transcription complexes, influencing gene

can be observed. To accomplish this, the expression in an unexpected way.

research team had to eliminate effects of ther-

mal radiation by carrying out the experiment pon exposure to changes in the envi- at target genes has been slowly gathering support

U

at a temperature of 0.1 K. Under these condi- ronment or to developmental cues dur- (1). On page 533 of this issue, Pokholok et al. (2)

tions, and using a technique called quantum ing differentiation, a cell reprograms report a global analysis in yeast of the associa-

jump spectroscopy, they could clearly see transcription in its nucleus through a circuitry tion of kinases with genes that they regulate, fur-

whether the electron was in the ground of signals that ultimately alters gene expres- ther supporting this model. Their findings sug-

cyclotron energy state, or had taken one, two, sion. Many of the steps of such signal-trans- gest that such interactions can be observed not

or more energy steps. ducing cascades are executed by kinases, only with sequence-specific transcription fac-

An intriguing feature of the one-electron enzymes that transfer phosphate molecules tors positioned at regulatory (promoter) regions

cyclotron is that the energy steps are not exactly onto target substrates. Often, kinases at the end lying upstream of target genes, but also with the

equal due to the relativistic shift of the electron s of such cascades (terminal kinases) trigger the coding region of genes in some cases.

mass with energy. One would hardly expect rel- necessary response by directly phosphorylat- The yeast HOG mitogen-activated protein

ativity to play a role at the ultralow energy of the ing transcription factors, coregulatory pro- kinase (MAPK) pathway responds to changes

one-electron cyclotron, but at the scale of preci- teins, or the proteins that, with DNA, make up in external osmolarity by activating the Hog1p

sion of the experiment, relativistic effects chromatin. Until recently, the prevailing view MAPK, which then regulates expression of

are important. Odom et al. measured g/2 = has been that terminal kinases operate enzy- osmoresponsive genes (3, 4). The necessity of

1.00115965218085, with an uncertainty of only matically, without stable association with the its transcription factor substrate to retain

7.6 parts in 1013, or 0.76 parts per trillion (1). chromatin that harbors target genes of a signal- Hog1p in the nucleus after cellular exposure to

Calculation of the electron moment anom- ing pathway. But an alternative model whereby osmotic stress suggested that Hog1p might

aly with the theory of QED presents a formida- such kinases also play a structural role by bind- form stable interactions with its substrates, and

ble challenge. The calculation involves evaluat- ing to factors within transcription complexes experiments that identified potential binding

ing the coefficients of terms in a power series, partners for Hog1p indicated the same (5, 6).

with each new term much more complex than A breakthrough came when chromatin

The authors are at the Nuclear Signalling Laboratory,

the previous one. The third-order term was cal- immunoprecipitation (ChIP) experiments show-

Department of Biochemistry, University of Oxford, Oxford

culated in the mid-1990s (8). The fourth-order ed that in response to osmotic stress, Hog1p is

OX1 3QU, UK. E-mail: abql4t@r.postjobfree.com

449

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