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new world has nearly 50% of its mass in water found. Meanwhile, precise Doppler measure- of the two DNA strands, called the leading
surrounding an Fe/Ni core and a silicate mantle ments may reveal the gravitational wobbles of strand. The lagging strand must be made in
(Fig. 1). It probably has an extraordinarily deep stars caused by Earth-like planets in tight orbits. shorter pieces that are joined together later.
ocean, which would be liquid given its equi- Most promising is NASA’s Kepler mission. These pieces, or Okazaki fragments, are a few
librium surface temperature of some 190 °C Launched in March 2009, Kepler is monitor- thousand bases in length and each is made
due to heating from the host star. A sauna-like ing 100,000 stars and is able to detect dimming every few seconds.
steam atmosphere is possible, with slow photo- as small as one part in ten thousand of their The second rule is that a DNA polymerase
lytic and hydrodynamic loss of that atmosphere normal brightness, rendering truly Earth-sized cannot start a DNA chain — it can only extend
caused by ultraviolet-light irradiation. A thin planets easily detectable. And someday, great a pre-existing DNA or RNA chain, called a
H/He outer atmosphere is also possible. space-borne interferometers (such as NASA’s primer. So all cells have a specialized enzyme,
And so comes the profound anthropocentric Space Interferometry Mission) and enormous the primase, that makes the first RNA primer
question. If this planet is 50% water, is it really cameras will be launched, able to detect, image for each DNA chain. A new primer must there-
kin of our Earth? Or did it form in a manner and spectroscopically analyse the landscapes, fore be made every few seconds to be used for
similar to that of Saturn or Neptune, with a oceans and atmospheres of nearby rocky Okazaki-fragment synthesis on the lagging-
rocky core that acquired large amounts of ices planets. These techniques will surely answer strand template. This single-stranded template
and gas gravitationally? By contrast, Earth has the question Aristotle, Epicurus and Demo- DNA is produced by the helicase, a component
only 0.06% water, and very little H and He gas, critus posed 2,400 years ago regarding Earth’s of the replisome that, in bacteria, moves in a
having formed in a dry environment. This new unique status in the Universe. ■ 5ʹ to 3ʹ direction to separate the two strands of
planet is close to Earth in size, but perhaps not Geoffrey Marcy is in the Department of the double helix (Fig. 1). And herein lies the
next of kin. Astronomy, University of California at Berkeley, problem — the primase needs to be associated
Nonetheless, Charbonneau’s team1 has high- Berkeley, California 94720, USA. with the helicase to function, but the primers
lighted a promising future for the discovery of e-mail: gmarcy@berkeley.edu on the lagging strand are made in the direc-
Earth-like worlds. Their efforts are just begin- 1. Charbonneau, D. Nature 462, 891–894 (2009). tion opposite to the movement of the heli-
ning, with smaller and rockier planets yet to be 2. Lépine, S. Astron. J. 130, 1680–1692 (2005). case. Moreover, primer synthesis is relatively
sluggish, taking about a second or so.
There are three possible solutions to the
replisome’s problem. One is for the whole repli-
DNA REPLICATION some to pause while the primer on the lagging
strand is made, then to resume its work; such
Prime-time looping pauses have been reported by the van Oijen
group3 during primer synthesis by the bacterial
virus (bacteriophage) T7 replisome (Fig. 2a).
Nicholas E. Dixon The second solution is for the primase, once
When the replication machinery copies DNA, it must unwind the double clamped onto the lagging-strand template
by the helicase, to be promptly released to
helix in one direction while synthesis of one of the strands proceeds in the make its primer at leisure, as happens with the
other. Making transient DNA loops may solve this directional dilemma. Escherichia coli replisome4 (Fig. 2b).
The third solution is for the replisome to
If you are a cell about to divide, you will first 3b 5b
continue leading-strand synthesis while the
need to use a multi-protein machine called a 5b 3b helicase–primase complex takes its time to
Okazaki
replisome to simultaneously make copies of fragment make the primer. The helicase continues to
both strands of your chromosomal DNA so Template unwind DNA in the forward direction while
DNA
that one strand can be passed to each daugh- the physically linked primase makes a primer
ter cell. Replisomes have long been thought to Helicase in the opposite direction. This arrangement
couple synthesis of both DNA strands by form- produces a transient single-stranded DNA
ing a ‘trombone loop’ of DNA that expands Polymerase
loop in the lagging-strand template, termed the
and relaxes as synthesis takes place discontinu- priming loop, which is subsequently released
ously on one of the strands. Two papers, one 3b to become part of the trombone loop when
by Pandey et al.1 on page 940 of this issue and 3b Primase the primer is passed to the lagging-strand
another by Manosas et al.2 published in Nature polymerase (Fig. 2c).
Chemical Biology, show that a second type of Lagging-strand The new reports1,2 use elegant single-mol-
‘trombone loop’
loop, called the ‘priming loop’, is transiently ecule experiments to provide the first direct
produced in the replisome. Leading Primer experimental evidence for priming-loop for-
strand 5b
The replisome faces special challenges as mation by the bacteriophage T7 and T4 repli-
it makes new DNA at rates that can approach somes. Pandey et al.1 worked with the whole
3b 5b Priming site
1,000 nucleotides per second. Unlike the T7 replisome, which has an unusual structure
machines that make proteins and RNA, which Figure 1 | DNA replication by a minimal replisome. in that its primase and helicase are part of the
work relatively sluggishly and in a linear fash- During DNA replication by the replisome same protein, so primase release is impossible.
ion, the replisome must simultaneously copy components, the DNA strands are separated by The authors used short DNA templates that
two strands of DNA that are aligned in oppo- the helicase enzyme and replicated by the leading- were already primed on the leading strand,
site directions (5ʹ to 3ʹ and 3ʹ to 5ʹ). Replisome and lagging-strand DNA polymerases. As DNA with priming sites (DNA sequences required
can be copied only in the 5ʹ to 3ʹ direction, the
chemistry obeys two rules. The first is that for primer synthesis) on the lagging strand.
polymerase continuously copies the leading
a DNA polymerase (the component of the strand, but the lagging strand is made in shorter Although lagging-strand primer synthesis
replisome that synthesizes new DNA from a pieces, or Okazaki fragments, that are joined occurred about 50% of the time, synthesis of
template strand) can extend the newly formed together later. DNA synthesis begins by extending the leading strand showed no sign of pausing
DNA chain only in the 5ʹ to 3ʹ direction. This a nucleic-acid primer that is synthesized at while a primer was made. Next, the authors1
means that it can continuously copy only one priming sites by the primase enzyme. employed a technique called fluorescence
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