repair-mediated degrada-
tion of stalled forks. The TET2
product 5-hydroxymethyl-
cytosine at stalled replication
forks recruited a base excision
repair–associated endonucle-
ase. Without TET2, stalled
replication forks were stabilized
instead of degraded, thereby
reducing PARP inhibitor sensi-
tivity. —LKF
Sci. Signal. 13 , eaba8091 (2020).CANCER IMMUNOLOGY
Phages and cancer
immunity
Gut bacteria are involved in
the education of T cell immune
responses, and the intestinal
ecosystem influences antican-
cer immunity. Fluckiger et al.
report microbial antigens that
might cross-react with antigensMICROBIOLOGY
How uromodulin helps
flush out bacteria
Urinary tract infections (UTIs)
are one of the most frequent
bacterial infections in humans.
The glycoprotein uromodulin
is the most abundant urinary
protein and can provide some
protection from UTIs, but the
precise mechanism has been
unclear. Weiss et al. found that
uromodulin forms stacked,
fishbone-like filaments that
act as a multivalent decoy
for bacterial pathogens with
adhesive pili that attach to the
uromodulin glycans (see the
Perspective by Kukulski). The
resulting uromodulin-pathogen
aggregates prevent bacterial
adhesion to glycoproteins of the
urinary epithelium and promote
pathogen clearance as urine is
excreted. This innate protec-
tion against UTIs is likely to be
particularly important in infants
and children. —SMH
Science, this issue p. 1005;
see also p. 917CANCER
A deeper look at cancer
immunity
A key goal in oncology is diag-
nosing cancer early, when it is
more treatable. Despite decades
of progress, early diagnosis
of asymptomatic patients
remains a major challenge.
Most methods involve detecting
cancer cells or their DNA, but
Beshnova et al. suggest a differ-
ent approach that is focused on
the body’s immune response.
The authors reasoned that the
presence of cancer may causealterations in the T cell recep-
tor repertoire, which could then
be detected. They designed a
deep-learning method for dis-
tinguishing the T cell repertoires
in the blood of patients with and
without cancer, which they vali-
dated in samples from multiple
clinical cohorts. —YN
Sci. Transl. Med. 12 , eaaz3738 (2020).MOLECULAR BIOLOGY
A fork in the road for drug
resistance
Inhibitors of the enzyme
poly(ADP-ribose) polymerase
(PARP) block the repair and
restart of stalled replication
forks, which eventually kills
cancer cells. Kharat et al. found
that the DNA demethylase TET2
was critical for sensitivity to
PARP inhibitors by promoting CREDITS (FROM TOP): REYESET AL.; CHRISTOPH NEHRBASS-AHLES, UNIVERSITY OF CAMBRIDGE930 21 AUGUST 2020 • VOL 369 ISSUE 6506 sciencemag.org SCIENCE
RESEARCH
Remote C–H borylation by
a modular iridium catalyst
Reyes et al.,p. 970Tiny gas bubbles visible in a freshly drilled ice core provide evidence
of atmospheric composition 330,000 to 450,000 years ago.IN SCIENCE JOURNALS
Edited by Michael FunkGLOBAL CARBON CYCLEPulses of the past
B
ursts of carbon dioxide, released into the atmo-
sphere and occurring on centennial time scales,
were seen during the cold periods of the last
glacial cycle but not in older or warmer condi-
tions. Nehrbass-Ahles et al. present a record of
atmospheric carbon dioxide concentrations retrieved
from the European Project for Ice Coring in Antarctica
Dome C ice core showing that these carbon dioxide
jumps occurred during both cold and warm periods
between 330,000 and 450,000 years ago. They relate
these pulses to disruptions of the Atlantic meridi-
onal overturning circulation caused by freshwater
discharge from ice sheets. Such rapid carbon dioxide
increases could occur in the future if global warming
also disrupts this ocean circulation pattern. —HJS
Science, this issue p. 1000Published by AAAS