Profiling DNA damage response following mitotic perturbations
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Profiling DNA damage response following mitotic perturbations. / Pedersen, Ronni Sølvhøi; Karemore, Gopal; Gudjonsson, Thorkell; Rask, Maj-Britt; Neumann, Beate; Hériché, Jean-Karim; Pepperkok, Rainer; Ellenberg, Jan; Gerlich, Daniel W; Lukas, Jiri; Lukas, Claudia.
In: Nature Communications, Vol. 7, 13887, 15.12.2016.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Profiling DNA damage response following mitotic perturbations
AU - Pedersen, Ronni Sølvhøi
AU - Karemore, Gopal
AU - Gudjonsson, Thorkell
AU - Rask, Maj-Britt
AU - Neumann, Beate
AU - Hériché, Jean-Karim
AU - Pepperkok, Rainer
AU - Ellenberg, Jan
AU - Gerlich, Daniel W
AU - Lukas, Jiri
AU - Lukas, Claudia
PY - 2016/12/15
Y1 - 2016/12/15
N2 - Genome integrity relies on precise coordination between DNA replication and chromosome segregation. Whereas replication stress attracted much attention, the consequences of mitotic perturbations for genome integrity are less understood. Here, we knockdown 47 validated mitotic regulators to show that a broad spectrum of mitotic errors correlates with increased DNA breakage in daughter cells. Unexpectedly, we find that only a subset of these correlations are functionally linked. We identify the genuine mitosis-born DNA damage events and sub-classify them according to penetrance of the observed phenotypes. To demonstrate the potential of this resource, we show that DNA breakage after cytokinesis failure is preceded by replication stress, which mounts during consecutive cell cycles and coincides with decreased proliferation. Together, our results provide a resource to gauge the magnitude and dynamics of DNA breakage associated with mitotic aberrations and suggest that replication stress might limit propagation of cells with abnormal karyotypes.
AB - Genome integrity relies on precise coordination between DNA replication and chromosome segregation. Whereas replication stress attracted much attention, the consequences of mitotic perturbations for genome integrity are less understood. Here, we knockdown 47 validated mitotic regulators to show that a broad spectrum of mitotic errors correlates with increased DNA breakage in daughter cells. Unexpectedly, we find that only a subset of these correlations are functionally linked. We identify the genuine mitosis-born DNA damage events and sub-classify them according to penetrance of the observed phenotypes. To demonstrate the potential of this resource, we show that DNA breakage after cytokinesis failure is preceded by replication stress, which mounts during consecutive cell cycles and coincides with decreased proliferation. Together, our results provide a resource to gauge the magnitude and dynamics of DNA breakage associated with mitotic aberrations and suggest that replication stress might limit propagation of cells with abnormal karyotypes.
U2 - 10.1038/ncomms13887
DO - 10.1038/ncomms13887
M3 - Journal article
C2 - 27976684
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 13887
ER -
ID: 172394745