The Literature
EDITOR’S CHOICETHE PAPER
B.W. Bauer et al., “Cohesin mediates DNA
loop extrusion by a ‘swing and clamp’
mechanism,” Cell, 184:5448–64, 2021.Approximately 2 meters of DNA is cram-
med into each of the human body’s cell
nuclei, themselves only about 10 mm in
diameter. To achieve this packaging feat,
DNA is wrapped around proteins to make
chromatin fibers, and further condensed
into tightly concertinaed loops. The forma-
tion and maintenance of these loops largely
depends on two protein complexes—cohe-
sin and condensin—each of which takes
charge at different phases of the cell cycle.
But how these complexes wrangle the
stringy chromatin into submission has to
this point been a bit of a black box.
Cohesin and condensin are ring-shaped
like donuts, leading researchers to propose
that chromatin might somehow thread
through their middles. But work by chro-
matin biologist Jan-Michael Peters of the
Research Institute of Molecular Pathol-ogy in Vienna, and colleagues now shows
that, in cohesin’s case at least, the protein
complex grabs DNA and pulls it, passing
it from one part of itself to another, much
like a person hauling rope might pass it
hand to hand.
It’s an “outstanding paper,” says Erez
Aiden, who studies genome folding at
Baylor College of Medicine but was not
involved in the research. It contains “by far
the best experiments to date... in terms
of the detailed mechanics of cohesin,” and
the results suggest that “we were way off
about the donut threading [idea],” he says.
To observe the movements of cohesin,
Peters’s team used specialized microscopy
techniques including high-speed atomic
force microscopy (HS-AFM), which enables
visualization of individual molecules in real
time, and single molecule f luorescence res-
onance energy transfer (smFRET), which
detects when molecules, or parts of mol-
ecules, come into close proximity. The
researchers also tested cohesin under an
assortment of conditions and with various
mutations to ascertain how these affected
cohesin’s movements, interactions within
the protein and with DNA, and the complex’s
ability to drive DNA loop formation. From
these analyses the researchers were able to
map the parts of cohesin that interact withDNA and piece together the likely stepwise
manner in which the DNA is manipulated.
The results suggest a specific chain of
events in the dance between cohesin and
DNA. First, cohesin’s “hinge” region binds
DNA and swings toward one of the protein
complex’s two “head” regions. The DNA is
then transferred to that head, which con-
verges with the other head to clamp the
DNA. Meanwhile the hinge swings back to
its original position readying itself to bind
another bit of DNA. In the hand-to-hand
rope-hauling analogy, the hinge is one hand
and the heads are the other.
This mechanism was inferred rather than
directly observed because, while both DNA
and cohesin were present in the smFRET
experiments and the loop assays, only the
cohesin was visible in the former and only
DNA in the latter. Also, the HS-AFM exper-
iments only contained cohesin. As a result,
says Aiden, questions remain about precisely
how the two interact and how loops arise.
Given that protein complexes related to
cohesin and condensin are found in all liv-
ing cells and regulate not only DNA pack-
aging but also gene functions, answering
these questions is of fundamental impor-
tance to understanding how the majority
of life forms operate, says Peters.
—Ruth WilliamsCELL BIOLOGYDynamics of a DNA-Packing Machine
DNA PULL: The hinge region of cohesin binds
DNA and swings toward one of the head regions.
The other head region then clamps down on the
DNA as the hinge is released to swing back to its
original position and bind a new part of the DNA.DNAHingeCohesinHeadsHINGE BINDING HINGE SWING HEAD CLAMPING HINGE RESET© NANOCLUSTERING.COMSPRING 2022 | THE SCIENTIST 63
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