sciencemag.org SCIENCERESEARCH
MAGNETISM
The ultimate in thin-film
magnetism
The alignment of the magnetic
properties of atoms gives rise
to a wealth of simple and exotic
properties that can be exploited.
As the dimension of the mate-
rial is reduced, such that the
atoms are in a single monolayer,
it was widely believed that
thermal fluctuations overwhelm
and prevent magnetic order-
ing. Gong and Zhang review
the developments that have
followed the recent discovery of
magnetism in two-dimensional
materials. Recognizing that
magnetic anisotropy can be
used to induce stable mag-
netism in atomic monolayers,
they provide an overview of
the materials available and the
physical understanding of the
effects and then discuss how
these effects could be exploited
for widespread practical appli-
cations. —ISO
Science, this issue p. 706
STRUCTURAL BIOLOGY
The machinery behind
amyloid peptides
b-Amyloid peptides, which are
derived from amyloid precursor
protein (APP), form the plaques
in the brain that are characteris-
tic of Alzheimer’s disease. Zhou
et al. report a high-resolution
structure of a transmembrane
segment of APP bound to human
g-secretase, the transmembrane
protease that cleaves APP to
give b-amyloid peptides (see
the Perspective by Lichtenthaler
and Güner). Disease-associated
mutations within presenilin-1,
the catalytic subunit of APP,
likely affect how the substrate is
bound and thus which peptides
are generated, with some being
more amyloidogenic. It may
now be possible to exploit the
features of substrate binding to
design inhibitors. —VV
Science, this issue p. 708;
see also p. 690
NEURODEGENERATION
How dipeptide repeats
cause pathology
A repeat expansion in the
chromosome 9 open reading
frame 72 (C9orf72) gene is the
most common known cause of
two neurodegenerative diseases:
frontotemporal dementia and
amyotrophic lateral sclerosis.
This expansion leads to the
abnormal production of proteins
of repeating dipeptides, but their
contribution to disease patho-
genesis remains unclear. Zhang
et al. engineered a mouse model
to study the consequences of
one of these dipeptides—proline-
arginine dipeptide repeat
protein, poly(PR)—in the brain.
They found that poly(PR) caused
neuron loss as well as motor and
memory impairments. These
detrimental effects resulted
from poly(PR)-induced per-
turbation of heterochromatin
function, a tightly packed form of
DNA that represses gene expres-
sion. —SMH
Science, this issue p. 707TOXINS
Bacterial warhead
targets DNA
The bacterial toxin colibactin
causes double-stranded DNA
breaks and is associated with
the occurrence of bacterially
induced colorectal cancer in
humans. However, isolation
of colibactin is difficult, and
its mode of action is poorly
understood. Wilson et al. studied
Escherichia coli that contain
the biosynthetic gene island
called pks, which is associated
with colibactin production (see
the Perspective by Bleich and
Arthur). They identified the
DNA adducts that resulted from
incubating pks+ E. coli in human
cells. To overcome the lack of
colibactin for direct analysis,
mimics of the pks product were
synthesized. From the resulting
synthetic adenine-colibactin
adducts, it became evident thatalkylation via a cyclopropane
“warhead” breaks the DNA
strands. Similar DNA adducts
were then identified in the gut
epithelia of mice infected with
pks+ E. coli. —CA
Science, this issue p. 709;
see also p. 689NANOMATERIALS
Cluster isomerization
Structural rearrangements at
the atomic scale can range from
isomerization of small molecules
to solid-solid phase transforma-
tions of crystals. Williamson et al.
show that magic-size cadmium
sulfide (CdS) crystalline clusters,
which are about 2 nanome-
ters in diameter and expose a
large fraction of surface atoms
capped by bidentate oleate
ligands, undergo a reversible
isomerization. The initial
a-Cd 37 S 20 phase, which has a
wurtzite-like crystal structure,
isomerizes to b-Cd 37 S 20 , which
has a zinc blende–like structure
upon exposure to methanol,
and then transforms back under
vacuum. This transition is driven
by distortion of the ligand shell
and shifts the excitonic energy
gap of the clusters. —PDS
Science, this issue p. 731GEOPHYSICS
Inferring blocked mantle
convection
The boundaries between rocks
with different physical proper-
ties in Earth’s interior come from
either a change in crystal struc-
ture or a change in chemical
composition. Wu et al. examined
the roughness of the boundary
between Earth’s upper and lower
mantle, thought to form from a
change in mineral structure (see
the Perspective by Houser). To
their surprise, in some locations,
the boundary has small-scale
roughness that requires some
chemical difference above
and below the boundary. This
observation provides evidence
of partially blocked mantlecirculation that leads to some
chemical differences between
the upper and lower mantle.
—BG
Science, this issue p. 736;
see also p. 696STRUCTURAL BIOLOGY
A human P spliceosome
structure
Splicing of some pre–messenger
RNAs could be regulated by cell
type–specific splicing factors.
Fica et al. describe the cryo–elec-
tron microscopy structure of the
human postcatalytic (P) spliceo-
some. Surprisingly, it lacks the
splicing factor Prp18, which plays
an essential role in exon ligation
in the yeast spliceosome. Instead,
a metazoan-specific splicing
factor, FAM32A, compensates
for Prp18 and promotes exon
ligation by penetrating the active
sites and directly stapling the 5′
exon and the 3′ splice site. These
findings suggest a way to control
tissue-specific alternative splic-
ing. —SYM
Science, this issue p. 710STRUCTURAL BIOLOGY
Getting over nucleosomal
barriers
In eukaryotic cells, RNA poly-
merase II (RNAPII) transcribes
DNA within nucleosome-coated
chromatin. The nucleosomes
can provide major roadblocks
for transcription. Cells solve
this problem by using transcrip-
tion elongation factors. Ehara
et al. solved the cryo–electron
microscopy structures of the
nucleosome-transcribing RNAPII
with elongation factors Elf1
and Spt4/5. Elf1 and Spt4/5
cooperatively suppress RNAPII
pausing at multiple super helical
locations [SHL(−6), SHL(−5),
and SHL(−2)] and facilitate
RNAPII progression through
SHL(−1) by adjusting the nucleo-
some position to favor forward
progression. —SYM
Science, this issue p. 744Edited by Stella Hurtley
ALSO IN SCIENCE JOURNALS705-B 15 FEBRUARY 2019 • VOL 363 ISSUE 6428
Published by AAAS