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@ARTICLE{Kolb:157333,
author = {T. Kolb$^*$ and U. Khalid$^*$ and M. Simović$^*$ and M.
Ratnaparkhe$^*$ and J. Wong$^*$ and A. Jauch and P.
Schmezer$^*$ and A. Rode$^*$ and S. Sebban and D. Haag$^*$
and M. Hergt$^*$ and F. Devens$^*$ and Y. Buganim and M.
Zapatka$^*$ and P. Lichter$^*$ and A. Ernst$^*$},
title = {{A} versatile system to introduce clusters of genomic
double-strand breaks in large cell populations.},
journal = {Genes, chromosomes $\&$ cancer},
volume = {60},
number = {5},
issn = {1098-2264},
address = {New York, NY},
publisher = {Wiley-Liss},
reportid = {DKFZ-2020-01562},
pages = {303-313},
year = {2021},
note = {#EA:B420#LA:B420#2021 May;60(5):303-313},
abstract = {In vitro assays for clustered DNA lesions will facilitate
the analysis of the mechanisms underlying complex genome
rearrangements such as chromothripsis, including the
recruitment of repair factors to sites of DNA double-strand
breaks. We present a novel method generating localized DNA
double-strand breaks using UV-irradiation with photomasks.
The size of the damage foci and the spacing between lesions
are fully adjustable, making the assay suitable for
different cell types and targeted areas. We validated this
set-up with genomically stable epithelial cells, normal
fibroblasts, pluripotent stem cells and patient-derived
primary cultures. Our method does not require a specialized
device such as a laser, making it accessible to a broad
range of users. Sensitization by BrdU incorporation is not
required, which enables analyzing the DNA damage response in
post-mitotic cells. Irradiated cells can be cultivated
further, followed by time-lapse imaging or used for
downstream biochemical analyses, thanks to the
high-throughput of the system. Importantly, we showed genome
rearrangements in the irradiated cells, providing a proof of
principle for the induction of structural variants by
localized DNA lesions. This article is protected by
copyright. All rights reserved.},
cin = {B420 / HD01 / B370 / B062 / B060},
ddc = {610},
cid = {I:(DE-He78)B420-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B370-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)B060-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32734664},
doi = {10.1002/gcc.22890},
url = {https://inrepo02.dkfz.de/record/157333},
}