Published December 30, 2013
In Focus
Text by Mitch Leslie
[email protected]
Sending sisters their separate ways
In Focus • THE JOURNAL OF CELL BIOLOGY
Downloaded from on June 18, 2017
THE JOURNAL OF CELL BIOLOGY
S
ister chromatids are often relucFOCAL POINT tant to separate during mitosis.
Germann et al. show that a protein
involved in DNA replication and repair
helps eliminate lingering connections that
can hold sister chromatids together (1).
Sister chromatids tangle almost every
time a cell enters mitosis. Unless the cell
releases these links, the structures can break
or fail to separate properly. Two kinds of (Clockwise from top left) Vibe Oestergaard, Susanne Germann, Irene Gallina, Michael Lisby,
attachments can persist even as late as and colleagues (not pictured) investigated four possible sources for the bridges between sister
anaphase (2). Chromatin bridges are the chromatids. They found that one mechanism promotes the formation of large chromatin bridges.
larger, better known variety. As their name Three mechanisms spur formation of the thinner ultrafine bridges. This time series shows an
ultrafine bridge (blue) as a chick cell advances through anaphase and telophase. Red marks the
indicates, they contain chromatin and chromosomes, and yellow marks TopBP1 attached to the bridge.
result when one sister chromatid adheres
to its sibling. In 2007 scientists discerned
The researchers also determined the
a second type of anaphase DNA entangle- suggesting that replication stress, a disrupment in mammalian cells: ultrafine bridges, tion in DNA synthesis, triggers production roles of Dpb11 during bridge formation and
breakdown. “What we show is that this proor UFBs (3). These thin filaments extend of UFBs.
between sister chromatids and don’t appear
Another possible source of bridges is tein binds both kinds of anaphase bridges,”
to contain chromatin. Some UFBs sport catenated DNA, in which both strands of says senior author Michael Lisby. But the
replication protein A, which latches onto one sister chromatid interweave with both protein has opposite effects on the two types
single DNA strands, suggesting that the strands of the other sister. Topoisomerase II of structures. Dpb11 inhibits chromatin
bridges are also single stranded (4). Sci- normally smoothes out these snarls, and bridges by curbing homologous recombientists have proposed four different ways the number of UFBs increased in cells nation. By contrast, the protein strengthens
in which anaphase bridges might arise. lacking this enzyme, the team found. The UFBs and enables them to elongate. Using
Germann et al. tested these ideas and how team also discovered that, in normal cells, chick cells, the researchers showed that the
cells deal with the entanglements.
topoisomerase II clusters on UFBs, indi- vertebrate equivalent of Dpb11, TopBP1,
The researchers started by identifying cating that the enzyme is hard at work to also performs dual functions, thwarting
chromatin bridges and stabilizing UFBs.
UFBs in budding yeast cells. Because the resolve these interconnections.
Those results raise a question: If TopBP1
nuclear envelope doesn’t break down durSome sisters aren’t that close, with
ing yeast mitosis, the structures extend only a single strand from each chromatid and Dpb11 stabilize UFBs, how do they
through a narrow tube that links the mother snarled. This hemicatenated DNA might spur chromosome separation? The researchand daughter nuclei. Like some UFBs in also generate UFBs. Germann et al. dis- ers speculate that stretching out UFBs might
mammalian cells, many yeast bridges abled the cell’s mechanism for dealing promote their eventual resolution by proappear to be single-stranded
with hemicatenated DNA viding access for topoisomerase II, which
DNA. The team found that
by deleting the gene for can disentangle the strands.
“What we show Sgs1, sparking an increase
A question for further research is what
UFBs are typically decois that [Dpb11] in UFBs.
happens after the bridges come down.
rated with the protein
Dpb11, which has several
Thus the study sup- Although anaphase bridges usually disapbinds both kinds
jobs, including detection
ports three of the potential pear before the end of mitosis, some DNA
of anaphase
and repair of DNA damage,
origins for UFBs—cate- damage persists into the next round of the
bridges.”
as well as DNA replication.
nated DNA, hemicatenated cell cycle. “It’s not clear how this damage is
One hypothesis holds
DNA, and unreplicated repaired,” says Lisby.
that anaphase bridges form at locations in sections of the genome. Germann et al.’s 1. Germann, S., et al. 2014. J. Cell Biol. http://
the genome that haven’t yet been repli- results discounted the fourth potential
dx.doi.org/10.1083/jcb.201305157.
cated or where DNA duplication has halted. source, the DNA repair mechanism homol- 2. Kaulich, M., F. Cubizolles, and E.A. Nigg. 2012.
Chromosoma. 121:395–408.
To evaluate this idea, Germann et al. dosed ogous recombination. The team discov3. Chan, K.L., P.S. North, and I.D. Hickson. 2007.
yeast cells with methyl methanesulfonate, ered that homologous recombination
EMBO J. 26:3397–3409.
which stops the advance of replication spurs the formation of chromatin bridges 4. Chan, K.L., and I.D. Hickson. 2009. Cell Cycle.
forks. The result was a surge in UFBs, but not UFBs.
8:3065–3066.
Photo courtesy of Leif Bolding
Repair protein helps resolve entanglements between sister chromatids.
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